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

Sebla B. Kutluay, Washington University School of Medicine in St. Louis
Ann Emery, University of North Carolina at Chapel Hill
Srinivasa R. Penumutchu, Case Western Reserve University
Dana Townsend, Washington University School of Medicine in St. Louis
Kasyap Tenneti, Washington University School of Medicine in St. Louis
Michaela K. Madison, Washington University School of Medicine in St. Louis
Amanda M. Stukenbroeker, Washington University School of Medicine in St. Louis
Chelsea Powell, The Rockefeller University
David Jannain, The Rockefeller University
Blanton S. Tolbert, Case Western Reserve University
Ronald I. Swanstrom, University of North Carolina at Chapel Hill
Paul D. Bieniasz, The Rockefeller University

Abstract

Alternative splicing of HIV-1 mRNAs increases viral coding potential and controls the levels and timing of gene expression. HIV-1 splicing is regulated in part by heterogeneous nuclear ribonucleoproteins (hnRNPs) and their viral target sequences, which typically repress splicing when studied outside their native viral context. Here, we determined the location and extent of hnRNP binding to HIV-1 mRNAs and their impact on splicing in a native viral context. Notably, hnRNP A1, hnRNP A2, and hnRNP B1 bound to many dispersed sites across viral mRNAs. Conversely, hnRNP H1 bound to a few discrete purine-rich sequences, a finding that was mirrored