Global dissociation of HuR-mRNA complexes promotes cell survival after ionizing radiation

Kiyoshi Masuda, Kotb Abdelmohsen, Mihee M. Kim, Subramanya Srikantan, Eun Kyung Lee, Kumiko Tominaga, Roza Selimyan, Jennifer L. Martindale, Xiaoling Yang, Elin Lehrmann, Yongqing Zhang, Kevin G. Becker, Jian Ying Wang, Hyeon Ho Kim, Myriam Gorospe

Research output: Contribution to journalArticlepeer-review


Ionizing radiation (IR) triggers adaptive changes in gene expression. Here, we show that survival after IR strongly depends on the checkpoint kinase Chk2 acting upon its substrate HuR, an RNA-binding protein that stabilizes and/or modulates the translation of target mRNAs. Microarray analysis showed that in human HCT116 colorectal carcinoma cells (WT), IR-activated Chk2 triggered the dissociation of virtually all of HuR-bound mRNAs, since IR did not dissociate HuR target mRNAs in Chk2-null (CHK2-/-) HCT116 cells. Accordingly, several HuR-interacting mRNAs encoding apoptosis- and proliferation-related proteins (TJP1, Mdm2, TP53BP2, Bax, K-Ras) dissociated from HuR in WT cells, but remained bound and showed altered post-transcriptional regulation in CHK2-/- cells. Use of HuR mutants that were not phosphorylatable by Chk2 (HuR(3A)) and HuR mutants mimicking constitutive phosphorylation by Chk2 (HuR(3D)) revealed that dissociation of HuR target transcripts enhanced cell survival. We propose that the release of HuR-bound mRNAs via an IR-Chk2-HuR regulatory axis improves cell outcome following IR.

Original languageEnglish (US)
Pages (from-to)1040-1053
Number of pages14
JournalEMBO Journal
Issue number6
StatePublished - Mar 16 2011
Externally publishedYes


  • Chk2
  • HuR phosphorylation
  • RNA-binding protein
  • radiotherapy
  • ribonucleoprotein complex

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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