PT  - JOURNAL ARTICLE
AU  - Manuel Garcia-Moreno
AU  - Marko Noerenberg
AU  - Shuai Ni
AU  - Aino I Järvelin
AU  - Esther González-Almela
AU  - Caroline Lenz
AU  - Marcel Bach-Pages
AU  - Victoria Cox
AU  - Rosario Avolio
AU  - Thomas Davis
AU  - Svenja Hester
AU  - Thibault J.M Sohier
AU  - Bingnan Li
AU  - Miguel A Sanz
AU  - Luis Carrasco
AU  - Emiliano P. Ricci
AU  - Vicent Pelechano
AU  - Bernd Fischer
AU  - Shabaz Mohammed
AU  - Alfredo Castello
TI  - Understanding RNP remodelling uncovers RBPs functionally required for viral replication
AID  - 10.1101/350686
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 350686
4099  - http://biorxiv.org/content/early/2018/06/20/350686.short
4100  - http://biorxiv.org/content/early/2018/06/20/350686.full
AB  - The compendium of RNA-binding proteins (RBPome) has been greatly expanded by the development of RNA-interactome capture (RNA-IC). However, it remains unknown how responsive is the RBPome and whether these responses are biologically relevant. To answer these questions, we created ‘comparative RNA-IC’ to analyse cells challenged with an RNA virus, called sindbis (SINV). Strikingly, the virus altered the activity of 245 RBPs, many of which were newly discovered by RNA-IC. Mechanistically, alterations in RNA binding upon SINV infection are caused by changes in the subcellular localisation of RBPs and RNA availability. Moreover, ‘RBPome’ responses are crucial, as perturbation of dynamic RBPs modulates the capacity of the virus to infect the cell. For example, ablation of XRN1 causes cells to be refractory to infection, while GEMIN5 moonlights as a novel antiviral factor. Therefore, RBPome remodelling provides a mechanism by which cells can extensively rewire gene expression in response to physiological cues.A quarter of the RBPome remodels upon SINV infection.The remodelling is caused by changes in protein localisation and RNA availability.Rewiring of the RBPome is crucial for viral infection efficacy.We discover RBPs with previously unknown anti- or pro-viral activity.HIGHLIGHTS