System-wide Profiling of RNA-Binding Proteins Uncovers Key Regulators of Virus Infection.

Molecular Cell
Manuel García-MorenoAlfredo Castello

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.

Citations

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Datasets Mentioned

BETA
PXD009789
GSE125182

Methods Mentioned

BETA
Infection
RNA-seq
immunoprecipitation
ubiquitination
iCLIP
PCR
transfection
Protein Assay
iCLIP-seq
chip

Key Resources (RRID) Mentioned

CVCL_0045
CVCL_1922
CVCL_U427
CVCL_1915

Software Mentioned

SAMtools depth
R package ggplot2
R package biomaRt
ImageJ
STRING
SAMtools merge
DESeq2
Bioconductor package biomaRt
cRIC
limma

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