Ben Blencowe及其同事发现，“盲肌样RNA结合蛋白” MBNL1 和 MBNL2是在胚胎干细胞和其他细胞类型之间被以不同方式调控的另类剪接事件的负调控因子。来自几个方面的证据表明，它们参与“胚胎干细胞样另类剪接模式”的调控。作者还发现了在成纤维细胞重新编程为诱导多能干细胞过程中的一个调控作用。(生物谷Bioon.com)
生物谷推荐英文摘要：
Nature doi:10.1038/nature12270
MBNL proteins repress ES-cell-specific alternative splicing and reprogramming
Hong Han, Manuel Irimia, P. Joel Ross, Hoon-Ki Sung, Babak Alipanahi,Laurent David, Azadeh Golipour,Mathieu Gabut,Iacovos P. Michael,Emil N. Nachman, Eric Wang,Dan Trcka,Tadeo Thompson,Dave O’Hanlon,Valentina Slobodeniuc,Nuno L. Barbosa-Morais, Christopher B. Burge, Jason Moffat, Brendan J. Frey,Andras Nagy,James Ellis,Jeffrey L. Wrana & Benjamin J. Blencowe
Previous investigations of the core gene regulatory circuitry that controls the pluripotency of embryonic stem (ES) cells have largely focused on the roles of transcription, chromatin and non-coding RNA regulators. Alternative splicing represents a widely acting mode of gene regulation, yet its role in regulating ES-cell 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 alternative splicing events that are differentially regulated between ES cells and other cell types. Knockdown of MBNL proteins in differentiated cells causes switching to an ES-cell-like alternative splicing pattern for approximately half of these events, whereas overexpression of MBNL proteins in ES cells promotes differentiated-cell-like alternative splicing patterns. Among the MBNL-regulated events is an ES-cell-specific alternative splicing 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 during somatic cell reprogramming.
