Journal article

Determination of RNA structural diversity and its role in HIV-1 RNA splicing

Phillip J Tomezsko, Vincent DA Corbin, Paromita Gupta, Harish Swaminathan, Margalit Glasgow, Sitara Persad, Matthew D Edwards, Lachlan Mcintosh, Anthony T Papenfuss, Ann Emery, Ronald Swanstrom, Trinity Zang, Tammy CT Lan, Paul Bieniasz, Daniel R Kuritzkes, Athe Tsibris, Silvi Rouskin

Nature | NATURE RESEARCH | Published : 2020

Abstract

Human immunodeficiency virus 1 (HIV-1) is a retrovirus with a ten-kilobase single-stranded RNA genome. HIV-1 must express all of its gene products from a single primary transcript, which undergoes alternative splicing to produce diverse protein products that include structural proteins and regulatory factors1,2. Despite the critical role of alternative splicing, the mechanisms that drive the choice of splice site are poorly understood. Synonymous RNA mutations that lead to severe defects in splicing and viral replication indicate the presence of unknown cis-regulatory elements3. Here we use dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) to investigate the structure of HIV..

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Grants

Awarded by NIH


Awarded by Center of HIV-1 RNA Studies (CRNA)


Funding Acknowledgements

The following reagents were obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: human recombinant IL-2 from M. Gately and HIV-1NL4-3 infectious molecular clone (pNL4-3) from M. Martin (cat. no. 114). This work was supported in part by the NIH (R21AI134365), the Center of HIV-1 RNA Studies (CRNA) NIH U54AI50470, the Smith Family Foundation and the Burroughs Wellcome fund.