System-wide Profiling of RNA-Binding Proteins Uncovers Key Regulators of Virus Infection
MOLECULAR CELL
Authors: Garcia-Moreno, Manuel; Noerenberg, Marko; Ni, Shuai; Jarvelin, Aino, I; Gonzalez-Almela, Esther; Lenz, Caroline E.; Bach-Pages, Marcel; Cox, Victoria; Avolio, Rosario; Davis, Thomas; Hester, Svenja; Sohier, Thibault J. M.; Li, Bingnan; Heikel, Gregory; Michlewski, Gracjan; Sanz, Miguel A.; Carrasco, Luis; Ricci, Emiliano P.; Pelechano, Vicent; Davis, Ilan; Fischer, Bernd; Mohammed, Shabaz; Castello, Alfredo
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.
A subset of SMN complex members have a specific role in tissue regeneration via ERBB pathway-mediated proliferation
NPJ REGENERATIVE MEDICINE
Authors: Pei, Wuhong; Xu, Lisha; Chen, Zelin; Slevin, Claire C.; Pettie, Kade P.; Wincovitch, Stephen; Burgess, Shawn M.; Barnabas, Beatrice B.; Black, Sean; Bouffard, Gerard G.; Brooks, Shelise Y.; Coleman, Holly; Dekhtyar, Lyudmila; Guan, Xiaobin; Han, Joel; Ho, Shi-ling; Legaspi, Richelle; Maduro, Quino L.; Masiello, Catherine A.; McDowell, Jennifer C.; Montemayor, Casandra; Mullikin, James C.; Park, Morgan; Riebow, Nancy L.; Schandler, Karen; Scharer, Chanthra; Schmidt, Brian; Sison, Christina; Stantripop, Sirintorn; Thomas, James W.; Thomas, Pamela J.; Vemulapalli, Meghana; Young, Alice C.
Abstract
Spinal muscular atrophy (SMA) is the most common genetic disease in children. SMA is generally caused by mutations in the gene SMN1. The survival of motor neurons (SMN) complex consists of SMN1, Gemins (2-8), and Strap/Unrip. We previously demonstrated smn1 and gemin5 inhibited tissue regeneration in zebrafish. Here we investigated each individual SMN complex member and identified gemin3 as another regeneration-essential gene. These three genes are likely pan-regenerative, since they affect the regeneration of hair cells, liver, and caudal fin. RNA-Seq analysis reveals that smn1, gemin3, and gemin5 are linked to a common set of genetic pathways, including the tp53 and ErbB pathways. Additional studies indicated all three genes facilitate regeneration by inhibiting the ErbB pathway, thereby allowing cell proliferation in the injured neuromasts. This study provides a new understanding of the SMN complex and a potential etiology for SMA and potentially other rare unidentified genetic diseases with similar symptoms.
COA
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