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
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Published in |
PLOS ONE, May 2015
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DOI | 10.1371/journal.pone.0125745 |
Pubmed ID | |
Authors |
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 |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 17% |
France | 1 | 17% |
Unknown | 4 | 67% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 5 | 83% |
Scientists | 1 | 17% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 2% |
United States | 1 | 2% |
Unknown | 54 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 19 | 34% |
Student > Bachelor | 9 | 16% |
Researcher | 6 | 11% |
Student > Master | 5 | 9% |
Student > Doctoral Student | 2 | 4% |
Other | 2 | 4% |
Unknown | 13 | 23% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 16 | 29% |
Biochemistry, Genetics and Molecular Biology | 15 | 27% |
Medicine and Dentistry | 4 | 7% |
Neuroscience | 2 | 4% |
Psychology | 2 | 4% |
Other | 4 | 7% |
Unknown | 13 | 23% |