Functional study of long noncoding RNA SAM in skeletal muscle stem cells and muscle regeneration
Invited conference paper presented and published in conference proceedings

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AbstractLong non-coding RNAs (lncRNAs) are novel family of gene regualtors but the study of lncRNAs in satellite cell lineage progression is still at the infancy stage. Here we identified a novel lncRNA, SAM (Sugt1 associated muscle lncRNA) that was enriched in the activated myoblast cells, but decreased as the cells progress to differentiation. Gain- or loss- of function of SAM in C2C12 myoblasts or muscle satellite cells altered myogenic proliferation and differentiation. Global deletion of SAM based on the KO-first strategy had no effect on normal muscle development and the mice showed no obvious phenotypic defects. However, it caused delay in postnatal muscle regeneration after BaCl2 induced acute damage and exacerbated the chronic injury induced dystrophic phenotype in the mdx mouse model. Consistently, inducible deletion of SAM in adult satellite cells led to impaired acute injury-induced muscle regeneration as evidenced by a marked reduction of the regenerated myofibers. Further examination of SCs revealed that SAM loss resulted in cell autonomous defects in cell activation/proliferation and promoted SCs precocious differentiation. Mechanistic probing through genome-wide profiling of transcriptomic changes revealed that knockdown of SAM using siRNA led to down-regulation of genes involved in cell cycle/division, kinetochore assembly and chromosome segregation. Simultaneously, it also up regulated muscle differentiation related gene expression. Furthermore, we found loss of SAM caused defective kinetochore assembly characterized by chromosome mis-alignment, disorganized spindle structures and a prolonged prometaphase-like arrest during SCs mitosis as well as destabilized kinetochore microtubules after cold treatment. Finally, we demonstrated SAM regulated the stability of Sugt1 (suppressor of G2 allele of SKP1), a co-chaperon protein key to kinetochore assembly through their physical interaction with each other in myoblast cells. Altogether, our findings identified SAM as a regulator of skeletal muscle regeneration and SC proliferation through modulating Sugt1 mediated kinetochore assembly.
All Author(s) ListYuying Li, Fengyuan Chen, Suyang Zhang, Jie Yuan, Hao Sun, Huating Wang
Name of ConferenceFASEB Science Research Conference 2018: Skeletal Muscle Satellite Cells and Regeneration
Start Date of Conference08/07/2018
End Date of Conference13/07/2018
Place of ConferenceSteamboat, Colorado
Country/Region of ConferenceUnited States of America
LanguagesEnglish-United States

Last updated on 2019-10-06 at 12:54