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.

doi:10.1101/2021.10.06.463443

bioRxiv · 10.1101/2021.10.06.463443

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.

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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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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.. 2021-10-07. seRNA PAM-1 regulates skeletal muscle satellite cell activation and aging through trans regulation of Timp2 expression synergistically with Ddx5. https://doi.org/10.1101/2021.10.06.463443

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