学术报告
题目：Discovery and Characterization of Factors Controlling Embryonic Stem Cell - Specific Alternative Splicing
报告人：Hong Han
The Donnelly Centre
University of Toronto
时间：2013年6月18日（周二）下午2点
地点：BIOPIC大会议室
报告摘要：
Previous investigations of the core gene regulatory circuitry that controls embryonic stem cell (ESC) pluripotency have largely focused on the roles of transcription, chromatin and non-coding RNA regulators. Alternative splicing (AS) represents a widely acting mode of gene regulation, yet its role in regulating ESC pluripotency and differentiation is poorly understood. Here, we identify the muscleblind-like RNA binding proteins, MBNL1 and MBNL2, as conserved and direct negative regulators of a large program of cassette exon AS events that are differentially regulated between ESCs and other cell types. Knockdown of MBNL proteins in differentiated cells causes switching to an ESC-like AS pattern for approximately half of these events, whereas over-expression of MBNL proteins in ESCs promotes differentiated cell-like AS patterns. Among the MBNL-regulated events is an ESC-specific AS switch in the forkhead family transcription factor FOXP1 that controls pluripotency. Consistent with a central and negative regulatory role for MBNL proteins in pluripotency, their knockdown significantly enhances the expression of key pluripotency genes and the formation of induced pluripotent stem cells (iPSCs) during somatic cell reprogramming.
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