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

TY - JOUR

T1 - Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function

AU - de Morree, Antoine

AU - Klein, Julian D.D.

AU - Gan, Qiang

AU - Farup, Jean

AU - Urtasun, Andoni

AU - Kanugovi, Abhijnya

AU - Bilen, Biter

AU - Van Velthoven, Cindy T.J.

AU - Quarta, Marco

AU - Rando, Thomas A.

N1 - Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PY - 2019/11

Y1 - 2019/11

N2 - 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.

AB - 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.

KW - SATELLITE CELLS

UR - http://www.scopus.com/inward/record.url?scp=85074718182&partnerID=8YFLogxK

U2 - 10.1126/science.aax1694

DO - 10.1126/science.aax1694

M3 - Journal article

C2 - 31699935

SN - 0036-8075

VL - 366

SP - 734

EP - 738

JO - Science

JF - Science

IS - 6466

ER -