Cell Communication and Signaling (Jan 2023)

LncRNA-TBP mediates TATA-binding protein recruitment to regulate myogenesis and induce slow-twitch myofibers

  • Manting Ma,
  • Bolin Cai,
  • Zhen Zhou,
  • Shaofen Kong,
  • Jing Zhang,
  • Haiping Xu,
  • Xiquan Zhang,
  • Qinghua Nie

DOI
https://doi.org/10.1186/s12964-022-01001-3
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 16

Abstract

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Abstract Background Skeletal muscle is comprised of heterogeneous myofibers that differ in their physiological and metabolic parameters. Of these, slow-twitch (type I; oxidative) myofibers have more myoglobin, more mitochondria, and higher activity of oxidative metabolic enzymes compared to fast-twitch (type II; glycolytic) myofibers. Methods In our previous study, we found a novel LncRNA-TBP (for “LncRNA directly binds TBP transcription factor”) is specifically enriched in the soleus (which has a higher proportion of slow myofibers). The primary myoblast cells and animal model were used to assess the biological function of the LncRNA-TBP in vitro or in vivo. Meanwhile, we performed a RNA immunoprecipitation (RIP) and pull-down analysis to validate this interaction between LncRNA-TBP and TBP. Results Functional studies demonstrated that LncRNA-TBP inhibits myoblast proliferation but promotes myogenic differentiation in vitro. In vivo, LncRNA-TBP reduces fat deposition, activating slow-twitch muscle phenotype and inducing muscle hypertrophy. Mechanistically, LncRNA-TBP acts as a regulatory RNA that directly interacts with TBP protein to regulate the transcriptional activity of TBP-target genes (such as KLF4, GPI, TNNI2, and CDKN1A). Conclusion Our findings present a novel model about the regulation of LncRNA-TBP, which can regulate the transcriptional activity of TBP-target genes by recruiting TBP protein, thus modulating myogenesis progression and inducing slow-twitch fibers. Video Abstract

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