%0 Journal Article
%T Interactome of the HIV-1 proteome and human host RNA.
%A Schynkel T
%A Snippenberg WV
%A Verniers K
%A Jang GM
%A Krogan NJ
%A Mestdagh P
%A Vandekerckhove L
%A Trypsteen W
%J EMBO Rep
%V 0
%N 0
%D 2024 Aug 9
%M 39122863
%F 9.071
%R 10.1038/s44319-024-00222-6
%X The human immunodeficiency virus (HIV-1) is highly dependent on a variety of host factors. Beside proteins, host RNA molecules are reported to aid HIV-1 replication and latency maintenance. Here, we implement multiple workflows of native RNA immunoprecipitation and sequencing (nRIPseq) to determine direct host RNA interaction partners of all 18 HIV-1 (poly)proteins. We identify 1,727 HIV-1 protein - human RNA interactions in the Jurkat cell line and 1,558 interactions in SupT1 cells for a subset of proteins, and discover distinct cellular pathways that seem to be used or controlled by HIV-1 on the RNA level: Tat binds mRNAs of proteins involved in the super elongation complex (AFF1-4, Cyclin-T1). Correlation of the interaction scores (based on binding abundancy) allows identifying the highest confidence interactions, for which we perform a small-scale knockdown screen that leads to the identification of three HIV-1 protein binding RNA interactors involved in HIV-1 replication (AFF2, H4C9 and RPLP0).