System-wide profiling of RNA-binding proteins uncovers key regulators of virus infection

Manuel Garcia-Moreno, Marko Noerenberg, Shuai Ni, Aino I. Järvelin, Esther González-Almela, Caroline E. Lenz, Marcel Bach-Pages, Victoria Cox, Rosario Avolio, Thomas Davis, Svenja Hester, Thibault J.M. Sohier, Bingnan Li, Gregory Heikel, Gracjan Michlewski, Miguel A. Sanz, Luis Carrasco, Emiliano P. Ricci, Vicent Pelechano, Ilan DavisBernd Fischer, Shabaz Mohammed, Alfredo Castello

Research output: Contribution to journalArticlepeer-review

Abstract

The compendium of RNA-binding proteins (RBPs) has been greatly expanded by the development of RNA-interactome capture (RIC). However, it remained unknown if the complement of RBPs changes in response to environmental perturbations and whether these rearrangements are important. To answer these questions, we developed “comparative RIC” and applied it to cells challenged with an RNA virus called sindbis (SINV). Over 200 RBPs display differential interaction with RNA upon SINV infection. These alterations are mainly driven by the loss of cellular mRNAs and the emergence of viral RNA. RBPs stimulated by the infection redistribute to viral replication factories and regulate the capacity of the virus to infect. For example, ablation of XRN1 causes cells to be refractory to SINV, while GEMIN5 moonlights as a regulator of SINV gene expression. In summary, RNA availability controls RBP localization and function in SINV-infected cells.
Original languageEnglish
Pages (from-to)196-211.e11
Number of pages27
JournalMolecular Cell
Volume74
Issue number1
Early online date21 Feb 2019
DOIs
Publication statusPublished - 4 Apr 2019

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