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Media type:
E-Article
Title:
Transcriptional start site heterogeneity modulates the structure and function of the HIV-1 genome
Contributor:
Kharytonchyk, Siarhei;
Monti, Sarah;
Smaldino, Philip J.;
Van, Verna;
Bolden, Nicholas C.;
Brown, Joshua D.;
Russo, Emily;
Swanson, Canessa;
Shuey, Alex;
Telesnitsky, Alice;
Summers, Michael F.
Published:
Proceedings of the National Academy of Sciences, 2016
Published in:
Proceedings of the National Academy of Sciences, 113 (2016) 47, Seite 13378-13383
Language:
English
DOI:
10.1073/pnas.1616627113
ISSN:
0027-8424;
1091-6490
Origination:
Footnote:
Description:
Significance Current dogma states that the integrated HIV type 1 provirus encodes a single RNA transcript that serves as both mRNA for generating viral proteins and as genomic RNA that is packaged and used for reverse transcription. We now show that multiple transcripts with different functions are generated in infected cells, a consequence of heterogeneous transcriptional start site usage. Transcripts that begin with a single capped guanosine are specifically selected for packaging, whereas those that begin with two or three capped guanosines are enriched on polysomes and used for translation. In vitro studies with recombinant 5′-leader transcripts reveal a mechanism by which the incorporation of a single 5′ guanosine dramatically alters the structure, function, and fate of the viral RNA.