14 Uridine Insertion/Deletion RNA Editing as a Paradigm for Site-specific Modifications of RNA Molecules

Abstract

A sense of wonderment at the variety, complexity, and beauty of natural phenomena is, I believe, the defining characteristic of our species. I wonder at the very existence of the universe, at physical laws and what they mean, and at the marvelous emergent properties in the complexities of living systems. In particular, the trypanosomatid protists caught my imagination many years ago and never let go. Wonder after wonder emerged from the study of these creatures, with the most striking being RNA editing. Uridine insertion/deletion RNA editing was discovered by Benne et al (1986). Four non-encoded U’s were found in the mRNA at the site of an evolutionarily conserved frameshift in the cytochrome oxidase subunit II gene which was encoded in the maxicircle mitochondrial DNA of trypanosome protists. Subsequent examples encompassed different trypanosome species and genes and included multiple U-insertions and U-deletions (Feagin et al. 1988; Shaw et al. 1988, 1989; Van der Spek et al. 1988), including the dramatic case of the pan-edited genes in which hundreds of U’s were inserted and deleted at hundreds of sites throughout the gene (Bhat et al. 1990; Koslowsky et al. 1990; Maslov et al. 1992). The mechanism of editing began to be revealed upon discovery of short guide RNAs (gRNAs) encoded both in the maxicircle DNA and in the thousands of catenated minicircle molecules; the gRNAs were perfectly complementary to completely edited mRNAs (Blum et al. 1990; Blum and Simpson 1990; Pollard et al. 1990; Sturm and Simpson 1990). Based on the presence...