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RNA Editing

Occasionally researches encounter a gene with a sequence of nucleotides that does not match exactly that in its RNA product:

If the product is mRNA, some of the codons in the open reading frame (ORF) of the gene specify different amino acids from those in the protein translated from the mRNA of the gene.

The reason is RNA editing: the alteration of the sequence of nucleotides in the RNA RNA editing occurs by two distinct mechanisms:

Substitution Editing

Example: the human APOB gene

Humans have a single locus encoding the APOB gene.
DNA can also be edited. B cells express another cytidine deaminase (called activation-induced deaminase or AID) that is essential for both class switch recombination (CSR) and somatic hypermutation (SHM) of antibody genes. Humans with disabling mutations in the gene for this enzyme produce only IgM antibodies. However, here the enzyme is acting on DNA, not RNA. In attempting to repair the mismatch formed (dC•dG converted to dU•dG), the normal DNA repair machinery of the cell produces CSR or SHM as the situation warrants. (This process is also responsible for the occasional aberrant translocation of the heavy-chain gene segments to a proto-oncogene. The result is a B-cell cancer — a lymphoma or leukemia.)

Some other examples of substitution editing

Insertion/Deletion Editing

Example: the gene (in the mitochondria of Trypanosoma brucei) for one of the subunits of cytochrome c oxidase

Link to a view of mitochondrial genes.

Several genes encoded in the mitochondrial DNA of this species (the cause of sleeping sickness in humans) encode transcripts that must be edited to make the mRNA molecules that will be translated into protein.

Editing requires a special class of RNA molecules called guide RNA (gRNA).

These small molecules have sequences that are complementary to the region around the site to be edited.

The guide RNA base-pairs — as best it can — with this region.

(Note that in addition to the usual purine-pyrimidine pairing of C-G and A-U, G-U base-pairing can also occur.)

Because of the lack of precise sequence complementarity, bulges occur either The bulges are eliminated by cutting the backbone of the shorter molecule and inserting complementary bases. Note that in the example shown here, the insertion of 4 nucleotides has created a frameshift so that the amino acids encoded downstream (after Val) in the edited RNA are entirely different from those specified by the gene itself.

Some other examples of insertion/deletion editing

Insertion/deletion editing has also been found occur with

Why RNA Editing?

Good question. Some possibilities:

So RNA editing appears to be here to stay. In fact, defects in RNA editing are associated with some human cancers as well as with amyotrophic lateral sclerosis (ALS — "Lou Gehrig's disease").

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6 March 2012