Post-transcriptional Modifications (RNA Processing)

Overview

Transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription

Genetic information from DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure is copied into messenger RNA Messenger RNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure ( mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure).

• In this process, mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure is synthesized from the 5’ end to the 3’ end.
• The initial transcript is known as heterogeneous nuclear RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure (hnRNA) or pre-mRNA.

Modifications

Primary transcripts, or immediate products of transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription, undergo alterations to become biologically functional.

• mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure:
  • Prokaryotes: Most primary mRNAs have no modifications.
  • Eukaryotes: Synthesized transcript of mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure (or hnRNA) undergoes processing before leaving the nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles.
    • Addition of 5’ cap
    • Addition of 3’ poly-A tail
    • Splicing
  • Modification of hnRNA produces mature mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure, which is transported to the cytoplasm through nuclear pores.
  • In some cases, RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure editing occurs with base changes, creating a sequence different from that copied from the DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure.
  • A different mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure sequence produces a different protein; this varies from the old hypothesis Hypothesis A hypothesis is a preliminary answer to a research question (i.e., a “guess” about what the results will be). There are 2 types of hypotheses: the null hypothesis and the alternative hypothesis. Statistical Tests and Data Representation of  “one gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics–one polypeptide.”
• Transfer RNA Transfer RNA The small RNA molecules, 73-80 nucleotides long, that function during translation to align amino acids at the ribosomes in a sequence determined by the mRNA (messenger RNA). There are about 30 different transfer RNAs. Each recognizes a specific codon set on the mRNA through its own anticodon and as aminoacyl tRNAs, each carries a specific amino acid to the ribosome to add to the elongating peptide chains. RNA Types and Structure ( tRNA tRNA The small RNA molecules, 73-80 nucleotides long, that function during translation (translation, genetic) to align amino acids at the ribosomes in a sequence determined by the mRNA (RNA, messenger). There are about 30 different transfer rnas. Each recognizes a specific codon set on the mRNA through its own anticodon and as aminoacyl trnas (RNA, transfer, amino Acyl), each carries a specific amino acid to the ribosome to add to the elongating peptide chains. RNA Types and Structure) and ribosomal RNA Ribosomal RNA The most abundant form of RNA. Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. Individual chains are conventionally designated by their sedimentation coefficients. In eukaryotes, four large chains exist, synthesized in the nucleolus and constituting about 50% of the ribosome. RNA Types and Structure ( rRNA rRNA The most abundant form of RNA. Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. Individual chains are conventionally designated by their sedimentation coefficients. In eukaryotes, four large chains exist, synthesized in the nucleolus and constituting about 50% of the ribosome. RNA Types and Structure): 
  • Structural molecules that are not translated
  • Both have pre-tRNAs and pre-rRNAs that undergo processing.

Addition of the 5′ Cap and 3′ Poly-A Tail

5′ cap

7-Methylguanosine (methylated guanylyl residue) is added to the 5’ end of hnRNA via:

• Removal of the leading phosphate group Phosphate group Nucleic Acids at the 5’ terminal by RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure triphosphatase
• Transfer of guanosine monophosphate Guanosine monophosphate A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature. Purine and Pyrimidine Metabolism (GMP) from the guanosine triphosphate group by guanylyl transferase
• Methylation Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. . Glucocorticoids of guanine Guanine Nucleic Acids by guanine-7-methyltransferase (methyl group from S-adenosylmethionine ( SAM SAM Anterior displacement of the mitral valve during systole. Hypertrophic Cardiomyopathy))

Functions:

• Prevents exonuclease degradation
• Recognition sequence for translation Translation Translation is the process of synthesizing a protein from a messenger RNA (mRNA) transcript. This process is divided into three primary stages: initiation, elongation, and termination. Translation is catalyzed by structures known as ribosomes, which are large complexes of proteins and ribosomal RNA (rRNA). Stages and Regulation of Translation

3′ Poly-A tail

50 to 250 adenylyl residues (AMP) are added to the 3’ end of hnRNA via:

• Cleaving of about 20 nucleotides Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. Nucleic Acids downstream from an AAUAA recognition sequence
• Addition (and extension Extension Examination of the Upper Limbs up to 250 nucleotides Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. Nucleic Acids) of poly-A tail (generated from ATP) by poly-A polymerase

Function:

• Prevents degradation in the cytosol Cytosol A cell’s cytoskeleton is a network of intracellular protein fibers that provides structural support, anchors organelles, and aids intra- and extracellular movement. The Cell: Cytosol and Cytoskeleton by 3′ exoribonucleases
• Stabilizes mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure

Heterogeneous Nuclear RNA Splicing

Exons and introns

Heterogeneous nuclear (pre-mRNA) contains:

• Coding sections called exons (expressed sequences)
• Noncoding sections called introns (intervening sequences)

Processing:

• hnRNA needs processing (splicing) to produce the mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure carrying the proper coding sequences.
• Occurs in most eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure, most commonly on mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure

Splicing

• Removal of introns from the hnRNA/pre-mRNA, while linking the exons to form the mature mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure
• Process involves the hnRNA and additional components:
  • Small nuclear ribonucleoproteins (which are made up of small nuclear RNAs (snRNAs) and proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis)
  • Other binding proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
• Junctions where splicing reaction occurs:
  • Splice sites: 
    • Areas where cuts are made between the exon and intron 
    • Base sequences identify these sites, one at the 5’ side (beginning of the intron) and the other at the 3’ side (end of the intron).
    • 5’ site/donor splice site: invariant GU
    • 3’ site/acceptor splice site: invariant AG AG Metabolic Acidosis 
  • Branch site: located upstream from 3’ site
• Mechanism:
  1. Small nuclear ribonucleoproteins recognize the splice sites and branch site owing to the base sequences on the hnRNA.
  2. hnRNA, small nuclear ribonucleoproteins, and other proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis combine to form the spliceosome. 
  3. The spliceosome complex makes a cut on the 5’ donor splice site (occurs via a nucleophilic attack by an adenylyl residue in the branch site).
  4. The now free 5’ terminus of the intron links to the branch site, forming a loop, or lariat, structure.
  5. The 3’ splice site is recognized, and the second cut occurs there. Release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of the lariat follows, and the 2 exons are joined to form the mature RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure
• Occurs simultaneously with the 5’ cap and 3’ poly-A tail hnRNA modifications 
• Related conditions:
  • β-Thalassemia: 
    • Contains defects in mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure splicing of β-globin gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics
    • Significant homozygous mutations ( thalassemia Thalassemia Thalassemia is a hereditary cause of microcytic hypochromic anemia and results from a deficiency in either the α or β globin chains, resulting in hemoglobinopathy. The presentation of thalassemia depends on the number of defective chains present and can range from being asymptomatic to rendering the more severely affected patients to be transfusion dependent. Thalassemia major) result in transfusion-dependent anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
  • Spinal muscle atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation:
    • Lack of functioning SMN1 Smn1 Spinal Muscular Atrophy gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics due to mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations
    • The remaining SMN2 Smn2 Spinal Muscular Atrophy is unable to compensate because of the defect at the level of pre-mRNA splicing (skipping of exon 7).

Alternative splicing

• Differential splicing of one hnRNA sequence
• Mechanisms:
  • Exons are selectively included or excluded.
  • Alternative 5′ donor or 3′ acceptor sites are used.
  • Polyadenylation sites can differ.
• Up to 95% of multi-exon genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure undergo alternative splicing (AS) to encode proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis with different cellular functions.
• AS is a rapidly responsive regulation step needed for fine-tuning protein synthesis Synthesis Polymerase Chain Reaction (PCR) and thereby determining cell phenotypes and proliferation rates.
• Approximately 15% of hereditary diseases and cancers are reported to be associated with AS.
• Different combinations of exons can lead to different related proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis being created from the same hnRNA:
  • Immunoglobulin molecules ( genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure for heavy chains Heavy chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kda. Immunoglobulins: Types and Functions have exons related to individual subtypes)
  • Tropomyosin Tropomyosin A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. Skeletal Muscle Contraction variants in muscle
  • Dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification (D2 receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors with 2 isoforms)

RNA Editing

Generally, the DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure sequence is reflected in the mature mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure. Alteration of the sequence or RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure editing is an exception.

Definition

• A change in the coding information after transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription results in the sequence of RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure differing from that of its original DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure.
• Believed to contribute to genetic regulation
• Processes:
  • Base changes
  • Base deletions
  • Base insertions

Base changes

“C-to-U” editing:

• Apolipoprotein B (apoB) gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics: The same gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics codes for ApoB100 (synthesized in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy) and ApoB48 (synthesized in the intestine).  
• In the intestine:
  • Deamination Deamination The removal of an amino group (NH2) from a chemical compound. Catabolism of Amino Acids of cytosine Cytosine A pyrimidine base that is a fundamental unit of nucleic acids. Nucleic Acids (to uracil Uracil One of four nucleotide bases in the nucleic acid RNA. Nucleic Acids) catalyzed by the enzyme cytidine deaminase.
  • CAA (cytidine– adenine Adenine A purine base and a fundamental unit of adenine nucleotides. Nucleic Acids– adenine Adenine A purine base and a fundamental unit of adenine nucleotides. Nucleic Acids) codon Codon A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal. Most codons are universal, but some organisms do not produce the transfer RNAs complementary to all codons. These codons are referred to as unassigned codons. Basic Terms of Genetics (in the mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure) → UAA (uridine– adenine Adenine A purine base and a fundamental unit of adenine nucleotides. Nucleic Acids– adenine Adenine A purine base and a fundamental unit of adenine nucleotides. Nucleic Acids), a termination signal or a stop codon Codon A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal. Most codons are universal, but some organisms do not produce the transfer RNAs complementary to all codons. These codons are referred to as unassigned codons. Basic Terms of Genetics
• As a result of this editing:
  • ApoB100 is a 100-kDa protein made of 4536 amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids.
  • ApoB48 is a shortened 48-kDa protein made of 2152 amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids.
  • The change produces ApoB48, which lacks the C-terminal domain of ApoB100 (responsible for LDL receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors binding).

“A-to-I” editing:

• Affects double-stranded RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure substrates
• Deamination Deamination The removal of an amino group (NH2) from a chemical compound. Catabolism of Amino Acids of adenine Adenine A purine base and a fundamental unit of adenine nucleotides. Nucleic Acids (to hypoxanthine) catalyzed by ADARs (adenosine deaminase acting on RNA)
• Adenosines converted into inosines, which leads to A-to-G base substitutions
• Generates alternative splice sites

Insertions/deletions

• Occur in trypanosomes and related protozoa Protozoa Nitroimidazoles, affecting the mitochondrial mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure
• Involves addition or deletion of uridine

Ribosomal RNA and Transfer RNA Processing

Ribosomal RNAs

• In prokaryotes:
  • As studied in Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli, 3 types of rRNAs (5S, 16S, and 23S) have polycistronic primary transcripts.
  • Initial processing of transcript via endonucleolytic cleavage by RNases → pre-rRNA
  • The 5’ and 3’ ends of pre-rRNA are then trimmed by another set of RNases.
  • Methylation Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. . Glucocorticoids occurs during assembly of ribosomes Ribosomes Multicomponent ribonucleoprotein structures found in the cytoplasm of all cells, and in mitochondria, and plastids. They function in protein biosynthesis via genetic translation. The Cell: Organelles to protect from degradation.
• In eukaryotes, primary transcript is a large 45S precursor molecule: 
  • Contains rRNA rRNA The most abundant form of RNA. Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. Individual chains are conventionally designated by their sedimentation coefficients. In eukaryotes, four large chains exist, synthesized in the nucleolus and constituting about 50% of the ribosome. RNA Types and Structure molecules (28S, 18S, and 5.8S) with spacer sequences in between
  • Processed in the nucleolus Nucleolus Within most types of eukaryotic cell nucleus, a distinct region, not delimited by a membrane, in which some species of rRNA are synthesized and assembled into ribonucleoprotein subunits of ribosomes. In the nucleolus rRNA is transcribed from a nucleolar organizer, i.e., a group of tandemly repeated chromosomal genes which encode rRNA and which are transcribed by RNA polymerase I. The Cell: Organelles:
    • By methylation Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. . Glucocorticoids at numerous sites (facilitated by small nucleolar RNAs (snoRNAs))
    • Then by cleaving and trimming of the RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure
  • Fourth type of rRNA rRNA The most abundant form of RNA. Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. Individual chains are conventionally designated by their sedimentation coefficients. In eukaryotes, four large chains exist, synthesized in the nucleolus and constituting about 50% of the ribosome. RNA Types and Structure, 5S, is processed separately.
  • The resultant mature rRNAs, which associate with other proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis, become the scaffold of the ribosomal units in the cytoplasm.
• Some eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic rRNA rRNA The most abundant form of RNA. Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. Individual chains are conventionally designated by their sedimentation coefficients. In eukaryotes, four large chains exist, synthesized in the nucleolus and constituting about 50% of the ribosome. RNA Types and Structure have introns, and in those, pre-rRNAs are self-splicing (act as ribozymes).

Transfer RNAs Transfer RNAs The small RNA molecules, 73-80 nucleotides long, that function during translation to align amino acids at the ribosomes in a sequence determined by the mRNA (messenger RNA). There are about 30 different transfer RNAs. Each recognizes a specific codon set on the mRNA through its own anticodon and as aminoacyl tRNAs, each carries a specific amino acid to the ribosome to add to the elongating peptide chains. Stages and Regulation of Translation

• Transfer RNA Transfer RNA The small RNA molecules, 73-80 nucleotides long, that function during translation to align amino acids at the ribosomes in a sequence determined by the mRNA (messenger RNA). There are about 30 different transfer RNAs. Each recognizes a specific codon set on the mRNA through its own anticodon and as aminoacyl tRNAs, each carries a specific amino acid to the ribosome to add to the elongating peptide chains. RNA Types and Structure is a single polynucleotide made up of an average of 75 nucleotides Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. Nucleic Acids with unique characteristics:
  • Due to distinct folding, the 5’ end and 3’ end make up the acceptor stem.
  • The 3’ end also has a CCA ( cytosine Cytosine A pyrimidine base that is a fundamental unit of nucleic acids. Nucleic Acids– cytosine Cytosine A pyrimidine base that is a fundamental unit of nucleic acids. Nucleic Acids– adenine Adenine A purine base and a fundamental unit of adenine nucleotides. Nucleic Acids) sequence.
  • Has modified bases Bases Usually a hydroxide of lithium, sodium, potassium, rubidium or cesium, but also the carbonates of these metals, ammonia, and the amines. Acid-Base Balance such as inosine, dihydrouridine, and pseudouridine
• The precursor tRNA tRNA The small RNA molecules, 73-80 nucleotides long, that function during translation (translation, genetic) to align amino acids at the ribosomes in a sequence determined by the mRNA (RNA, messenger). There are about 30 different transfer rnas. Each recognizes a specific codon set on the mRNA through its own anticodon and as aminoacyl trnas (RNA, transfer, amino Acyl), each carries a specific amino acid to the ribosome to add to the elongating peptide chains. RNA Types and Structure contains:
  • Extra nucleotides Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. Nucleic Acids at the 3’ and 5’ ends
  • Introns
• Processing involves:
  • Removal of the extra nucleotides Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. Nucleic Acids and introns
  • Modification of standard bases Bases Usually a hydroxide of lithium, sodium, potassium, rubidium or cesium, but also the carbonates of these metals, ammonia, and the amines. Acid-Base Balance (such as methylation Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. . Glucocorticoids and deamination Deamination The removal of an amino group (NH2) from a chemical compound. Catabolism of Amino Acids)
  • Utilizes RNase P (a ribozyme) to form the 5’ end
  • Addition of CCA at the 3’ end by tRNA tRNA The small RNA molecules, 73-80 nucleotides long, that function during translation (translation, genetic) to align amino acids at the ribosomes in a sequence determined by the mRNA (RNA, messenger). There are about 30 different transfer rnas. Each recognizes a specific codon set on the mRNA through its own anticodon and as aminoacyl trnas (RNA, transfer, amino Acyl), each carries a specific amino acid to the ribosome to add to the elongating peptide chains. RNA Types and Structure nucleotidyltransferase