Unbiased identification of CSDE1-regulated targets during oncogene-induced senescence [i-CLIP]

We show that the RNA-binding protein CSDE1/UNR promotes oncogene-induced senescence (OIS) in primary mouse keratynocytes challenged by over-expression of H-RASv12. Depletion of CSDE1 leads to senescence bypass, cell immortalization and tumor formation. Combining individual nucleotide cross-linking and immunoprecipitation (iCLIP), RNA-seq and polysome profiling followed by functional studies, we identify targets regulated by CSDE1 and uncover the downstream molecular mechanisms. Overall design: iCLIP combined with high-throughput sequencing was used to generate a transcriptome-wide binding map of CSDE1 in primary mouse keratinocytes in resting conditions or upon oncogene-induced senescence.