tRNAs as primers and inhibitors of retrotransposons

Abstract

The functional relationship between tRNAs and retrotransposons have been known for more than 35 years. tRNAs are used as primer molecules to guide the reverse transcription of retrotransposons. Recently, tRNAs have also emerge as important players in the postranscriptional regulation of retrotransposons by means of tRNA-derived small RNAs. This surprisingly new layer of regulation indicates that tRNAs are used both in the promotion and the suppression of the reverse transcription of retrotransposons indicating their primary role in the life cycle of LTR retrotransposons. This adds another level of translational control to tRNAs. Here we review the different known levels of interactions of tRNAs and retrotransposons and highlight the unknown parts of this interaction.

Keywords: RNAi; retrotransposons; small RNAs; tRNA-derived fragments; tRNAs.

Figure 1.

Life cycle of a LTR retrotransposon and inhibition mediated by tRFs. A. Schematic representation of the main steps in the life cycle of a LTR retrotransposon. B. Schematic representation of the known interactions of tRFs with the life cycle of retrotransposons and the potential inhibitions at the posttranscriptional and reverse transcription levels. The gag, pol and env genes are depicted in the genomic sequence of the LTR retrotransposon. GAG: GAG protein produced from the gag gene that forms the virus-like particles inside which retrotranscription takes place. RT: retrotranscriptase protein encoded by the pol gene that mediates the retrotranscription of the LTR-retrotransposon RNA into DNA. INT: integrase protein coded by the pol gene that mediates the reintegration of the retrotranscribed DNA into the genome.

Figure 2.

LTR retrotransposon structure and reverse transcription process. A. Structure of a model LTR retrotransposon depicting the two long terminal regions (5′ and 3′ LTR), the gag, pol [with its three different enzymatic functions: protease (prot), retrotransciptase (rt) and integrase (int)] and env genes, the primer binding site (PBS) and the poly-purine tracts (PPT). B. Model of LTR retrotransposon reverse transcription process: (1) for most LTR retrotransposons and retroviruses 18 nts of the 3′ extreme of a mature tRNA interact with the PBS region of the Pol II transcript from the genomic LTR retrotransposon. (2) This interaction primes the synthesis of the unique 5′ sequence (U5) and a repeat sequence (R). (3) This initial transcript pairs with the R region on the 3′ extreme of the LTR retrotransposon transcript and (4) primes the transcription of the whole element. (5) The original RNA template is then degraded leaving only a fragment in the PPT region that (6) primes the second strand synthesis, first of the 3′ extreme which then moves to the 5′ region (7) where it pairs with the R and U5 regions and primes the final synthesis of the whole element. The final process gives rise to a dsDNA with two LTR that contain both the U3, R and U5 regions (8). The integrase coded by the pol gene inserts this dsDNA fragment within the chromosomal DNA.