Proteomics

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Long noncoding RNA SAM promotes myoblast proliferation through stabilizing Sugt1 and facilitating kinetochore assembly


ABSTRACT: Long non-coding RNAs (lncRNAs) are family of gene regulators but the functional study of lncRNAs in skeletal muscle satellite cells (SCs) remains at the infancy stage. Here we identify SAM (Sugt1 associated muscle) lncRNA (also known as Snhg15, (small nucleolar RNA host gene 15) that is enriched in the proliferating myoblast cells and down-regulated as the cells progressed to differentiation. Gain- or loss- of function of SAM in muscle SCs alters myogenic proliferation and differentiation. Global deletion of SAM based on the KO-first strategy has no overt effect on mice but impairs adult muscle regeneration following acute damage; the loss also exacerbates the chronic injury induced dystrophic phenotype in the mdx mouse model. Consistently, inducible deletion of SAM in adult SCs leads to deficiency in acute injury-induced muscle regeneration. Further examination of SCs revealed that SAM loss results in cell autonomous defect in proliferative expansion of myoblasts. Mechanistically, we find SAM interacts and stabilizes Sugt1 (suppressor of G2 allele of SKP1) protein, a co-chaperon protein key to kinetochore assembly during cell division. Loss of SAM or Sugt1 both cause disruptive kinetochore assembly and microtubule attachment in mitotic cells due to mis-localization of key components Dsn1 and Hec1 proteins. Altogether, our findings identify SAM as a regulator of SC proliferation through facilitating Sugt1 mediated kinetochore assembly during cell division.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Yuying LI  

LAB HEAD: Huating Wang

PROVIDER: PXD018147 | Pride | 2020-05-18

REPOSITORIES: Pride

Dataset's files

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F006316.dat Other
R14129-1.xls Xls
R14129_1_LU_1.mgf Mgf
R14129_1_LU_1.raw Raw
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Long noncoding RNA SAM promotes myoblast proliferation through stabilizing Sugt1 and facilitating kinetochore assembly.

Li Yuying Y   Yuan Jie J   Chen Fengyuan F   Zhang Suyang S   Zhao Yu Y   Chen Xiaona X   Lu Leina L   Zhou Liang L   Chu Ching Yan CY   Sun Hao H   Wang Huating H  

Nature communications 20200601 1


The functional study of lncRNAs in skeletal muscle satellite cells (SCs) remains at the infancy stage. Here we identify SAM (Sugt1 asssociated muscle) lncRNA that is enriched in the proliferating myoblasts. Global deletion of SAM has no overt effect on mice but impairs adult muscle regeneration following acute damage; it also exacerbates the chronic injury-induced dystrophic phenotype in mdx mice. Consistently, inducible deletion of SAM in SCs leads to deficiency in muscle regeneration. Further  ...[more]

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