Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function
Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function
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DOI：
10.1126/science.aax1694
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发表时间：
2019-11-08
期刊：
影响因子：
56.9
通讯作者：
Rando, Thomas A.
中科院分区：
文献类型：
--
作者：
de Morree, Antoine;Klein, Julian D. D.;Rando, Thomas A.
成体干细胞对组织内环境稳定至关重要。在骨骼肌中，肌肉干细胞（MuSC）处于静止状态，但对控制稳态周转的机制知之甚少。在这里，我们表明，在小鼠中，不同肌肉（例如，肢体与膈肌）之间MuSC激活率的变化是由转录因子Pax3的水平决定的。我们进一步表明，Pax3的水平是由其转录，这是由小的核仁RNA U1调节的替代聚腺苷酸化控制。Pax3信使RNA的3'非翻译区不同的同种型对microRNA miR206的调节差异敏感，这导致体内Pax3蛋白的不同水平。这些发现强调了一个以前未被认识的机制，即多个RNA种类对干细胞命运的稳态调节。
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.