Telomerase activity of reverse transcriptase.

Abstract

In their report “Reverse transcriptase motifs in the catalytic subunit of telomerase” ([25 Apr., p. 561][1]), Joachim Lingner et al . demonstrate that such motifs are present in the catalytic subunit of the telomerase that they purified and identified in Euplotes aediculatus . They show that similar motifs exist in a homologous yeast gene and that alteration of these motifs by classical yeast genetics affects telomere elongation. After mentioning that telomerases are frequently called “specialized reverse transcriptases,” they stress that three main features distinguish them from other reverse transcriptases: (i) telomerase uses only a small portion of its RNA subunit as a template; (ii) during processive synthesis of telomeric repeats, the substrate translocates from one end of the template to the other by an as-yet-unknown mechanism; and (iii) the telomerase protein is stably associated with its RNA subunit (a feature also found in retrotransposon reverse transcriptase). On the other hand, we have recently shown that, under specific in vitro conditions, human immunodeficiency virus–type 1 (HIV-1) reverse transcriptase uses a portion of its template RNA to perform a reiterative synthesis; the substrate then translocates from one end of the template motif to the other, and the enzyme maintains a stable association with its RNA ([1][2]). On specific template sequences, it is therefore sufficient to modify the cationic environment (from manganese chloride to magnesium chloride in the reaction buffer) in order to switch the HIV-1 reverse transcriptase mode of synthesis from a regular one to a telomerase-like reiterative synthesis (as described in figure 9 of the report by Lingner et al .). Thus, HIV-1 reverse transcriptase can display an appreciable telomerase-like activity, indicating that these enzymes are biochemically closely related. 1. [↵][3]1. M. Ricchetti, 2. H. Buc , Biochemistry 35, 14970 (1996). [OpenUrl][4][CrossRef][5][PubMed][6][Web of Science][7] [1]: /lookup/doi/10.1126/science.276.5312.561 [2]: #ref-1 [3]: #xref-ref-1-1 View reference 1 in text [4]: {openurl}?query=rft.jtitle%253DBiochemistry%26rft.volume%253D35%26rft.spage%253D14970%26rft_id%253Dinfo%253Adoi%252F10.1021%252Fbi961274v%26rft_id%253Dinfo%253Apmid%252F8942663%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [5]: /lookup/external-ref?access_num=10.1021/bi961274v&link_type=DOI [6]: /lookup/external-ref?access_num=8942663&link_type=MED&atom=%2Fsci%2F277%2F5328%2F883.7.atom [7]: /lookup/external-ref?access_num=A1996VV23700038&link_type=ISI