Abstract
HUMAN immunodeficiency virus gene expression is regulated transcriptionally and post-transcriptionally1–4 by the virally encoded tat protein (Tat). Tat functions through an RNA target sequence located in the untranslated region at the 5′ end of viral transcripts5–8. In Xenopus oocytes, translation of RNA containing the target sequence is specifically activated by Tat. This activation only occurs if the RNA is injected into the nucleus, and might be due to a Tat-dependent, nucleus-specific chemical modification of the RNA which somehow facilitates translation8. Here we demon-strate that Tat activation of its target RNA in the nucleus involves a Tat-dependent covalent modification. The modified RNA is com-petent for translation after reinjection into either the nucleus or the cytoplasm in the absence of Tat. Furthermore, we find that the nucleoside analogue 5,6-dichloro-l-β-D-ribofuranosylben-zimidazole, which inhibits processivity of RNA polymerase II (ref. 9), blocks this Tat-dependent modification.
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Braddock, M., Thorburn, A., Kingsman, A. et al. Blocking of Tat-dependent HIV-1 RNA modification by an inhibitor of RNA polymerase II processivity. Nature 350, 439–441 (1991). https://doi.org/10.1038/350439a0
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DOI: https://doi.org/10.1038/350439a0
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