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Label-free protein-RNA interactome analysis identifies khsrp signaling downstream of the p38/Mk2 kinase complex as a critical modulator of cell cycle progression

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Title:Label-free protein-RNA interactome analysis identifies khsrp signaling downstream of the p38/Mk2 kinase complex as a critical modulator of cell cycle progression
Creators Name:Boucas, J. and Fritz, C. and Schmitt, A. and Riabinska, A. and Thelen, L. and Peifer, M. and Leeser, U. and Nuernberg, P. and Altmüller, J. and Gaestel, M. and Dieterich, C. and Reinhardt, H.C.
Abstract:Growing evidence suggests a key role for RNA binding proteins (RBPs) in genome stability programs. Additionally, recent developments in RNA sequencing technologies, as well as mass-spectrometry techniques, have greatly expanded our knowledge on protein-RNA interactions. We here use full transcriptome sequencing and label-free LC/MS/MS to identify global changes in protein-RNA interactions in response to etoposide-induced genotoxic stress. We show that RBPs have distinct binding patterns in response to genotoxic stress and that inactivation of the RBP regulator module, p38/MK2, can affect the entire spectrum of protein-RNA interactions that take place in response to stress. In addition to validating the role of known RBPs like Srsf1, Srsf2, Elavl1 in the genotoxic stress response, we add a new collection of RBPs to the DNA damage response. We identify Khsrp as a highly regulated RBP in response to genotoxic stress and further validate its role as a driver of the G1/S transition through the suppression of Cdkn1aP21 transcripts. Finally, we identify KHSRP as an indicator of overall survival, as well as disease free survival in glioblastoma multiforme.
Keywords:Cultured Cells, Cyclin-Dependent Kinase Inhibitor p21, DNA Damage, Disease-Free Survival, ELAV-Like Protein 1, G1 Phase Cell Cycle Checkpoints, Gene Expression Profiling, Glioblastoma, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Protein Serine-Threonine Kinases, Ribonucleoproteins, RNA, RNA-Binding Proteins, Serine-Arginine Splicing Factors, Signal Transduction, Trans-Activators, p38 Mitogen-Activated Protein Kinases, Animals, Mice
Source:PLoS ONE
Publisher:Public Library of Science
Page Range:e0125745
Additional Information:Copyright © 2015 Boucas et al This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
Official Publication:https://doi.org/10.1371/journal.pone.0125745
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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