RNA Editing

Although RNA editing is really a form of processing of RNA it is usually categorized separately. One reason for this is that it was more recently discovered that the 3 classic processing events (5' CAP, splicing and polyadenylation) and another is that it does not appear to occur to all pre-mRNAs unlike the other three. Therefore we will consider it separately.

The editing of an mRNA is very specific although it is often the case that editing is limited to a certain cell type or developmental stage. A classic example is the editing ofapo-B mRNA in humans. In liver cells the mRNA is not edited and codes for a large protein of 4563 amino acids. However, in cells of the intestine there is a single C to U edit that generates a UAA codon (edited from a CAA codon). This creates a Stop codon and the edited mRNA only codes for a protein of 2153 amino acids.

RNA editing is a change in the nucleotide sequence following transcription. There are several types of editing:

• C to U editing by deamination
• A to I editing by deamination
• Uracil insertion based on a guide RNA (gRNA) template
• Uracil deletion based on a gRNA template

Here we will only cover C to U editing and Uracil insertion.

C-U editing: Certain transcripts are edited by the deamination of Cs at specific sites. The mechanism involves a site-specific deaminase that binds to the mRNA at the site to be edited by recognizes the structure and sequence at that location. The mechanism is illustrated below.

U insertion: Some transcripts are edited by the insertion of a number of Uracils at specific sites. This editing mechanism is based on the use of a guide RNA (gRNA) that is transcribed separately from the genome. The mRNA and the gRNA share complementarity over a certain stretch. The gRNA acts as a template: where there are unpaired Adenines in the gRNA a structure called an editosome forms and inserts Uracils into the mRNA at positions where there are unpaired Adenines in the gRNA. A separate editosome is used at each location where there is one or more contiguous unmatched Adenines. Although this diagram shows a single gRNA, in some cases, multiple gRNAs are required to edit a single mRNA at different locations. The basic mechanism is illustrated here: