seRNA PAM-1 regulates skeletal muscle satellite cell activation and aging through trans regulation of Timp2 expression synergistically with Ddx5
So, K. K. H.; Huang, Y.; Zhang, S.; He, L.; Li, Y.; Chen, X.; Zhao, Y.; Ding, Y.; Zhou, J.; Yuan, J.; Sham, M. H.; Sun, H.; Wang, H.
Show abstract
Muscle satellite cells (SCs) are responsible for muscle homeostasis and regeneration; and lncRNAs play important roles in regulating SC activities. Here in this study, we identify PAM-1 (Pax7 Associated Muscle lncRNA) that is induced in activated SCs to promote SC activation into myoblast cells upon injury. PAM-1 is generated from a myoblast specific super-enhancer (SE); as a seRNA it binds with a number of target genomic loci predominantly in trans. Further studies demonstrate that it interacts with Ddx5 to tether PAM-1 SE to it inter-chromosomal targets Timp2 and Vim to activate the gene expression. Lastly, we show that PAM-1 expression is increased in aging SCs, which leads to enhanced inter-chromosomal interaction and target genes up-regulation. Altogether, our findings identify PAM-1 as a previously unknown lncRNA that regulates both SC activation and aging through its trans gene regulatory activity.
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