Autor: |
Jorge Boucas, Christian Fritz, Anna Schmitt, Arina Riabinska, Lisa Thelen, Martin Peifer, Uschi Leeser, Peter Nuernberg, Janine Altmueller, Matthias Gaestel, Christoph Dieterich, H Christian Reinhardt |
Jazyk: |
angličtina |
Rok vydání: |
2015 |
Předmět: |
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Zdroj: |
PLoS ONE, Vol 10, Iss 5, p e0125745 (2015) |
Druh dokumentu: |
article |
ISSN: |
1932-6203 |
DOI: |
10.1371/journal.pone.0125745 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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