The term RNA editing
describes those molecular processes in which the information content in an RNA
molecule is altered through a chemical change in the base makeup. To date, such changes have been observed in tRNA
, and mRNA
molecules of eukaryotes
but not prokaryotes
. The demonstration of RNA editing in prokaryotes may only be a matter of time, considering the range of species in which the various RNA editing processes have been found. RNA editing occurs in the cell nucleus
, as well as in mitochondria
, which are thought to have evolved from prokaryotic-like endosymbionts
Most of the RNA editing processes, however, appear to be evolutionarily recent acquisitions that arose independently. The diversity of RNA editing mechanisms includes nucleoside modifications such as C to U and A to I deaminations, as well as non-templated nucleotide additions and insertions. RNA editing in mRNAs effectively alters the amino acid sequence of the encoded protein so that it differs from that predicted by the genomic DNA sequence.
Editing by insertion or deletion
RNA editing through the addition of uracil has been found in mitochondria from kinetoplastid protozoa. This uses a gRNA (guide RNA
) that is complementary of the region to be changed, with some differences. It binds to the region to be edited, and the differences are copied (by complementation) from the gRNA to the mRNA. This is typically seen in mitochondria
and the functional effect is often a frameshift
Editing by deamination
The editing involves cytidine deaminase that deaminates a cytidine
base into a uridine
base. An example of C to U editing is with the apolipoprotein B
gene in humans. Apo B100 is expressed in the liver and apo B48 is expressed in the intestines. The B100 form has a CAA sequence that is edited to UAA, a stop codon, in the intestines. It is unedited in the liver.
A to I editing occurs in regions of double stranded RNA (dsRNA). A to I editing can be specific (a single adenosine is edited within the stretch of dsRNA) or promiscuous (up to 50% of the adenosines are edited). Specific editing occurs within short duplexes (e.g. those formed in an mRNA where intronic sequence base pairs with a complementary exonic sequence), while promiscuous editing occurs within longer regions of duplex (e.g. pre- or pri-miRNAs, duplexes arising from transgene or viral expression, duplexes arising from paired repetitive elements). There are many effects of A to I editing, arising from the fact that I behaves as if it is G both in translation and when forming secondary structures. These effects include alteration of coding capacity, altered miRNA or siRNA target populations, heterochromatin formation, nuclear sequestration, cytoplasmic sequestration, endonucleolytic cleavage by Tudor-SN, inhibition of miRNA and siRNA processing and altered splicing.