a latent pro-survival function for the mir-290-295 cluster in mouse embryonic stem cells一个潜在pro-survival函数mir - 290 - 290集群在小鼠胚胎干细胞.pdfVIP

A Latent Pro-Survival Function for the Mir-290-295 Cluster in Mouse Embryonic Stem Cells 1,2,3.¤a 1,3,4. 1,3¤b 3,5 5 Grace X. Y. Zheng , Arvind Ravi , J. Mauro Calabrese , Lea A. Medeiros , Oktay Kirak , Lucas M. Dennis3,5¤c, Rudolf Jaenisch3,5, Christopher B. Burge2,3, Phillip A. Sharp1,3* 1 MIT Koch Institute for Integrative Cancer Research, Cambridge, Massachusetts, United States of America, 2 Computational and Systems Biology Graduate Program, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 3 Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 4 Harvard-MIT Health Sciences and Technology Program, Cambridge, Massachusetts, United States of America, 5 Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America Abstract MicroRNAs (miRNAs) post-transcriptionally regulate the expression of thousands of distinct mRNAs. While some regulatory interactions help to maintain basal cellular functions, others are likely relevant in more specific settings, such as response to stress. Here we describe such a role for the mir-290-295 cluster, the dominant miRNA cluster in mouse embryonic stem cells (mESCs). Examination of a target list generated from bioinformatic prediction, as well as expression data following miRNA loss, revealed strong enrichment for apoptotic regulators, two of which we validated directly: Caspase 2, the most highly conserved mammalian caspase, and Ei24, a p53 transcriptional target. Consistent with these predictions, mESCs lacking miRNAs were more likely to initiate apoptosis following genotoxic exposure