Ben Blencowe及其同事發(fā)現(xiàn),，“盲肌樣RNA結(jié)合蛋白” MBNL1 和 MBNL2是在胚胎干細(xì)胞和其他細(xì)胞類型之間被以不同方式調(diào)控的另類剪接事件的負(fù)調(diào)控因子,。來自幾個方面的證據(jù)表明，它們參與“胚胎干細(xì)胞樣另類剪接模式”的調(diào)控,。作者還發(fā)現(xiàn)了在成纖維細(xì)胞重新編程為誘導(dǎo)多能干細(xì)胞過程中的一個調(diào)控作用,。(生物谷Bioon.com)
生物谷推薦英文摘要：
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.
