seRNA PAM controls skeletal muscle satellite cell proliferation and aging through trans regulation of Timp2 expression synergistically with Ddx5.
Karl Kam Hei SoYile HuangSuyang ZhangYulong QiaoLiangqiang HeYuying LiXiaona ChenMai Har ShamHao SunHuating WangPublished in: Aging cell (2022)
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 (Pax7 Associated Muscle lncRNA) that is induced in activated/proliferating SCs upon injury to promote SC proliferation as myoblast cells. PAM 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 SE to its inter-chromosomal targets Timp2 and Vim to activate the gene expression. Lastly, we show that PAM expression is increased in aging SCs, which leads to enhanced inter-chromosomal interaction and target genes upregulation. Altogether, our findings identify PAM as a previously unknown lncRNA that regulates both SC proliferation and aging through its trans gene regulatory activity.
Keyphrases
- skeletal muscle
- poor prognosis
- induced apoptosis
- cell proliferation
- gene expression
- signaling pathway
- binding protein
- cell cycle arrest
- long non coding rna
- copy number
- genome wide
- insulin resistance
- dna methylation
- pi k akt
- cell death
- type diabetes
- cell cycle
- long noncoding rna
- drug induced
- genome wide identification
- bioinformatics analysis
- african american