Fidelity of Transcription (RNA Editing)

The informational content of gene transcripts can be altered during or after transcription by a process collectively called RNA editing. The information changes are carried out at the level of mRNA. RNA editing appears to be a widespread phenomenon for both normal and aberrant RNA processing in organelles and nuclei. It was first discovered in the mitochondria of kinetoplasts in protozoa. Two types of RNA editing have been observed: (1) alteration of coding sequence by nucleotide insertion and/ or deletion and (2) base substitution. In mammalian cells, editing of an individual base in mRNA can cause a change in the sequence of the protein. Such changes can occur by enzymatic deamination in which C is converted to U or A is converted to hypoxanthine. Change of U to C has also been observed in many plants. The (mitochondrial) mRNAs of several kinetoplastid species (Crithidia, Trypanosoma, etc.) were found to be edited by the insertion and deletion of U’s at many sites in mRNAs. The editing process uses a template consisting of a guideRNA(gRNA) whose genes function as independent transcription units. The gRNAs are generally 55–70 nucleotides in length and complementary to the mRNA for a significant distance including and surrounding the edited region. The gRNA dictates the specificity of uridine insertions by its pairing with the pre-edited RNA, but also provides the U residues that are inserted into the target RNA by transesterification reactions; the reaction proceeds along the pre-edited RNA in the 3´-5´ direction. The RNA editing process reveals the existence of a previously unrecognized level for the control of gene expression. Recognition of this process has resulted in an expansion of the central dogma. Multiple RNA editing processes play a significant role in normal physiological processes, as well as being responsible for some disease.