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Free keywords:
Animals
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21/genetics
DNA Damage/genetics
Disease-Free Survival
ELAV-Like Protein 1/genetics
G1 Phase Cell Cycle Checkpoints/*genetics
Gene Expression Profiling/*methods
Glioblastoma/genetics
Humans
Intracellular Signaling Peptides and Proteins/*genetics
Mice
Nuclear Proteins/genetics
Protein-Serine-Threonine Kinases/*genetics
RNA/*genetics
RNA-Binding Proteins/*genetics
Ribonucleoproteins/genetics
Signal Transduction/genetics
Trans-Activators/*genetics
p38 Mitogen-Activated Protein Kinases/*genetics
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 G(1/)S transition through the suppression of Cdkn1a(P21) transcripts. Finally, we identify KHSRP as an indicator of overall survival, as well as disease free survival in glioblastoma multiforme.
