Genome-Wide Analysis of Heterogeneous Nuclear Ribonucleoprotein (hnRNP) Binding to HIV-1 RNA Reveals a Key Role for hnRNP H1 in Alternative Viral mRNA Splicing

Author:

Kutluay Sebla B.1,Emery Ann2,Penumutchu Srinivasa R.3,Townsend Dana1,Tenneti Kasyap1,Madison Michaela K.1,Stukenbroeker Amanda M.1,Powell Chelsea4,Jannain David4,Tolbert Blanton S.3,Swanstrom Ronald I.256,Bieniasz Paul D.47

Affiliation:

1. Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, USA

2. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

3. Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, USA

4. Laboratory of Retrovirology, The Rockefeller University, New York, New York, USA

5. Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

6. UNC Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

7. Howard Hughes Medical Institute, The Rockefeller University, New York, New York, USA

Abstract

Alternative splicing of HIV-1 mRNAs is an essential yet quite poorly understood step of virus replication that enhances the coding potential of the viral genome and allows the temporal regulation of viral gene expression. Although HIV-1 constitutes an important model system for general studies of the regulation of alternative splicing, the inputs that determine the efficiency with which splice sites are utilized remain poorly defined. Our studies provide an experimental framework to study an essential step of HIV-1 replication more comprehensively and in much greater detail than was previously possible and reveal novel cis -acting elements regulating HIV-1 splicing.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of General Medical Sciences

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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