Primer tRNAs for reverse transcription.

Both retroviruses and long terminal repeat (LTR) retrotransposons use cellular tRNAs as primers for reverse transcription during their replication cycles. In retroviruses, primer tRNA is selectively packaged into the virion, where it is placed onto the primer binding site (PBS) of the viral RNA genome and used to prime the reverse transcriptase (RT)-catalyzed synthesis of minus-strand cDNA. Studies of how these processes are carried out in different retroviral groups have revealed both similarities and differences. Although less extensively studied, a comparison of processes occurring in LTR retrotransposons with similar processes occurring in retroviruses is also informative and is included herein. For an excellent summary of earlier work on retroviral primer tRNAs, the reader is referred to the review by Waters and Mullin (83). Later reviews on this topic include those by Litvak et al. (48), Marquet et al. (54), and Leis et al. (41), while reviews providing information on retrotransposon primer tRNAs include those by Voytas and Boeke (78) and Sandmeyer and Menees (68). Retroviruses can be divided into three major subfamilies, oncoviruses, lentiviruses, and spumaviruses, while retrotransposons can be placed into two categories named after the prototypic Drosophila elements copia and gypsy (68). The replication cycles of retroviruses and LTR retrotransposons show strong similarities, as shown in Fig. 1. Both retroviruses and retrotransposons code for Gag and Gag-Pol proteins. Retroviral Gag proteins contain sequences for matrix (MA), capsid (CA), and nucleocapsid (NC) proteins, while retrotransposon Gag proteins contain sequences for CA and, sometimes, NC proteins (68). Both retroviral and retrotransposon pol genes code for protease (PR), RT, and integrase (IN). copiaand gypsy-like elements can be distinguished from each other by major differences in RT sequences (89), and while in copia-like elements the IN gene precedes the RT-RNase H gene, in gypsy-like elements the RT-RNase H sequence precedes the IN sequence (18, 73), as in retroviruses. Many types of retroviruses have an extracellular stage in their life cycle, and this is associated with the presence of envelope protein (Env). The replication cycle of most retrotransposon elements produces an intracellular virus-like particle (VLP) which contains no Env protein. However, some gypsy elements do have an extracellular stage, and this is associated with the presence of Env protein (36, 60). Some of the similarities and differences among retroviruses and retrotransposons relevant to this review are summarized in Table 1. The full-length RNA transcribed from proviral or retrotransposon elements codes for Gag and Gag-Pol precursor proteins, which in the cytoplasm assemble into particles that package the full-length mRNA, as well as low-molecularweight tRNA. In both particle types, the Gag and Gag-Pol precursor proteins are cleaved by a viral protease to the final mature proteins. The reverse transcription of the packaged RNA in both retroviruses and retrotransposons is primed by a cellular tRNA, and the resulting double-stranded cDNA is integrated into the host cell DNA by viralor retrotransposonencoded IN.