Guide RNA

Guide RNAs (a.k.a. gRNA) are the RNAs that guide the insertion or deletion of uridine residues into mRNAs in kinetoplastid protists in a process known as RNA editing.

The phrase "guide RNA" and "gRNA" are also used in DNA editing in the case of Cas9

Trypanosomatid protists and other kinetoplastids have a novel post-transcriptional mitochondrial RNA modification process known as "RNA editing". The mitochondrial genome in these cells consists of 20-50 maxicircles that encode genes and "cryptogenes" (and some gRNAs) and 10-20,000 minicircles that encode gRNAs. All of these molecules are catenated into a giant network of DNA that is situated at the base of the flagellum in the inner compartment of the single mitochondrion.

A majority of the maxicircle transcripts can not be translated into proteins due to multiple frameshifts in the sequences. These frameshifts are corrected after transcription by the insertion and deletion of uridine residues at precise sites which create an open reading frame that is translated into a mitochondrial protein homologous to mitochondrial proteins from other cells. The insertions and deletions are mediated by short guide RNA (gRNAs) which encode the editing information in the form of complementary sequences (allowing GU as well as GC base pairs). The gRNAs are transcribed from both the maxicircles and the minicircles.

The presence of two genomes in the mitochondrion, one of which contains sequence information that corrects errors in the other genome, is novel. Editing proceeds generally 3' to 5' on the mRNA. The initial editing event occurs when a gRNA forms an RNA duplex with a complementary mRNA sequence just downstream of the editing site. This then recruits a number of ribonucleoprotein complexes that direct the precise insertions and deletions of uridine residues, thereby extending the duplex upstream. The adjacent upstream editing site is then modified in the same manner. A single gRNA usually encodes the information for several editing sites (an editing "block"), the editing of which produces a complete gRNA/mRNA duplex.

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