美国斯坦福大学医学院Thomas A. Rando、Antoine de Morree等研究人员合作取得一项新进展。他们发现转录因子Pax3的可变多腺苷酸化修饰控制肌肉干细胞（MuSC）的命运和肌肉功能。相关论文发表在2019年11月7日出版的《科学》上。

研究人员发现，在小鼠中，不同肌肉（例如，肢体肌肉与横隔膜肌肉）之间的MuSC激活率变化取决于转录因子Pax3的水平。研究人员进一步表明，Pax3的水平受其转录本可变多腺苷酸化的控制，而后者受小核仁RNA U1的调控。在其3'非翻译区不同的Pax3信使RNA的同工型对microRNA miR206的调节有不同的敏感性，这导致体内Pax3蛋白水平的变化。 这些发现强调了多种RNA种类对干细胞命运的稳态调控的未知机制。

据介绍，成人干细胞对于组织稳态至关重要。在骨骼肌中，MuSC处于静止状态，但对控制体内稳态转换的机制知之甚少。

附：英文原文

Title: Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function

Author: Antoine de Morree, Julian D. D. Klein, Qiang Gan, Jean Farup, Andoni Urtasun, Abhijnya Kanugovi, Biter Bilen, Cindy T. J. van Velthoven, Marco Quarta, Thomas A. Rando

Issue&Volume: Volume 366 Issue 6466

Abstract: Adult stem cells are essential for tissue homeostasis. In skeletal muscle, muscle stem cells (MuSCs) reside in a quiescent state, but little is known about the mechanisms that control homeostatic turnover. Here we show that, in mice, the variation in MuSC activation rate among different muscles (for example, limb versus diaphragm muscles) is determined by the levels of the transcription factor Pax3. We further show that Pax3 levels are controlled by alternative polyadenylation of its transcript, which is regulated by the small nucleolar RNA U1. Isoforms of the Pax3 messenger RNA that differ in their 3′ untranslated regions are differentially susceptible to regulation by microRNA miR206, which results in varying levels of the Pax3 protein in vivo. These findings highlight a previously unrecognized mechanism of the homeostatic regulation of stem cell fate by multiple RNA species.

DOI: 10.1126/science.aax1694

Source:https://science.sciencemag.org/content/366/6466/734