mRNA Editing

Abstract

The editing of messenger RNA transcripts respresents a recently identified processing event by which multiple RNA transcripts can be generated from a single genomic locus to increase the coding potential of the human genome.

Keywords: RNA processing; modification; deamination; receptor; protein diversity

Figure 1.

RNA editing by hydrolytic deamination. RNA editing events involving the conversion of cytidine to uridine (C to U) and adenosine to inosine (A to I) occur as a result of hydrolytic deamination at the C4 and C6 positions of the pyrimidine and purine bases, respectively, with the oxygen of water acting as the nucleophile. R: ribose.

Figure 2.

Biosynthetic pathway for the tissue‐specific production of apoB isoforms through site‐specific C‐to‐U editing. (a) Organization of the APOB gene, with the start (ATG), stop (TAA) and edited glutamine (CAA) codons indicated in exons 1, 26 and 29, respectively; the cytidine residue in the nonedited intestinal transcript and the uridine residue in the edited mRNA, after the C‐to‐U modification, are underlined. The structures of the apoB‐100 and apoB‐48 protein isoforms are shown below, with their principal functional domains and corresponding amino acid lengths. (A)n, poly(A) tail. (b) The tripartite sequence motif required for the C‐to‐U editing of APOB transcripts (efficiency element, spacer, mooring sequence), with the edited cytidine residue indicated in white on black lettering.

Figure 3.

RNA editing of 5‐HT2CR transcripts. (a) Representation of the amino acid sequence and predicted topology of the human 2C subtype of serotonin receptor. The positions of amino acid alterations in the second intracellular loop of the receptor, which result from A‐to‐I editing events, are indicated, along with possible amino acid residues that result from permutations of editing at five distinct sites. (b) Secondary structure of the region of major editing modifications in the pre‐mRNA transcript encoding the 5‐HT2CR, as predicted by RNA folding algorithms (Zuker, ); the positions of the five edited adenosine residues (labeled A–E) and the exon–intron boundary are indicated. The codons altered by RNA editing are emboldened and shaded to match the amino acid positions shown in (a).

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Further Reading

Bass BL (ed.) (2001) RNA Editing. New York, NY: Oxford University Press.

Grosjean H and Benne R (eds.) (1998) Modification and Editing of RNA. Washington, DC: ASM Press.

Papavasiliou FN and Schatz DG (2002) Somatic hypermutation of immunoglobulin genes: merging mechanisms for genetic diversity. Cell 109(supplement): S35–S44.

Web Links

5‐Hydroxytrypamine (serotonin) receptor 2C (HTR2C); LocusID: 3358. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3358

Apolipoprotein B (APOB); LocusID: 338. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=338

Glutamate receptor, metabotropic 5 (GRM5); LocusID: 2915. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2915

Neurofibromin 1 (NF1). LocusID: 4763. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4763

5‐Hydroxytrypamine (serotonin) receptor 2C (HTR2C); MIM number: 312861. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?312861

Apolipoprotein B (APOB); MIM number: 107730. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?107730

Glutamate receptor, metabotropic 5 (GRM5); MIM number: 604102. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?604102

Neurofibromin 1 (NF1) MIM number: 162200. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?162200

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Sansam, Christopher L, and Emeson, Ronald B(Sep 2005) mRNA Editing. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005041]