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Updated: Dec 21, 2025

An Integrated Approach for Microprotein Identification and Sequence Analysis
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The micropeptide LEMP plays an evolutionarily conserved role in myogenesis.

Lantian Wang1, Jing Fan1, Lili Han2

  • 1State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 200031, Shanghai, China.

Cell Death & Disease
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Researchers discovered a conserved micropeptide, LEMP, encoded by MyolncR4, that is crucial for muscle development and regeneration across species. This finding highlights the evolutionary importance of micropeptides in biological processes.

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • Micropeptides are increasingly recognized as key regulators in biological processes.
  • The functional conservation of micropeptides across species is largely unexplored.

Purpose of the Study:

  • To investigate the evolutionary conservation and functional roles of micropeptides in myogenesis.
  • To identify and characterize novel micropeptides involved in skeletal muscle differentiation.

Main Methods:

  • RNA-sequencing of mouse satellite cells and differentiated myotubes.
  • Bioinformatic analysis to identify conserved lncRNAs and potential micropeptide-encoding regions.
  • Functional studies in mouse and zebrafish models, including gene knockout and rescue experiments.

Main Results:

  • Identified MyolncR4 (1500011K16RIK) as a lncRNA upregulated during muscle differentiation, encoding a conserved 56-aa micropeptide named LEMP.
  • LEMP demonstrated pro-myogenic activity, promoting muscle formation and regeneration in mice.
  • LEMP is essential for zebrafish muscle development, with its absence causing defects that are rescued by mouse LEMP expression.
  • LEMP localizes to the plasma membrane and mitochondria, interacting with mitochondrial proteins.

Conclusions:

  • Uncovered an evolutionarily conserved micropeptide, LEMP, with critical roles in skeletal muscle differentiation and regeneration.
  • Demonstrated the functional importance of micropeptides in myogenesis across vertebrate species.
  • Highlighted LEMP's potential involvement in mitochondrial function during muscle development.