Translation initiation of non‐LTR retrotransposons by HDVlike self‐cleaving ribozymes

Abstract

Many non‐long terminal repeat (non‐LTR) retrotransposons lack internal promoters and are co‐transcribed with their host genes. These transcripts need to be liberated before inserting into new loci. Using structure‐based bioinformatics, we have recently shown that several classes of retrotransposons in phyla spanning arthropods, nematodes, and chordates utilize self‐cleaving ribozymes of the hepatitis delta virus (HDV) family for processing their 5′ termini. Ribozyme‐terminated retrotransposons include rDNA‐specific R2, R4 and R6; telomere‐specific SART; and Baggins and RTE elements. The R2 and R6 ribozymes were recently shown to promote translation initiation of downstream open reading frames in translation reactions in vitro with rabbit reticulocyte lysate and they also demonstrate in vivo activity in Drosophila S2 cell transfections. Translation initiation now extends to other retrotransposon‐associated ribozymes including those that do not insert site‐specifically. Additionally, mutagenesis and deletion experiments have been used to establish the functions of various parts of the ribozyme in ribosome binding and translation. Novel roles, such as those presented here, highlight the biological importance of self‐cleaving ribozymes as well as functional RNAs in general.