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LARP4 is an RNA-binding protein that binds nuclear-encoded mitochondrial mRNAs to promote mitochondrial function

Benjamin M Lewis1,2,3,4, Chae Yun Cho4, Hsuan-Lin Her1,2,3,5

  • 1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92037, USA.

RNA (New York, N.Y.)
|January 2, 2024
PubMed

Insights

LARP4 is a novel RNA-binding protein regulating mitochondrial function. It binds nuclear-encoded mitochondrial mRNAs (NEMmRNAs), promoting respiratory chain and ribosome protein production for cellular energy.

Area of Science:

  • Mitochondrial Biology
  • Molecular Cell Biology
  • RNA Biology

Background:

  • Mitochondria-associated RNA-binding proteins (RBPs) are crucial for mitochondrial biogenesis and homeostasis.
  • The specific RBPs that regulate nuclear-encoded mitochondrial mRNAs (NEMmRNAs) are largely unknown.

Purpose of the Study:

  • To systematically identify RBPs that bind and regulate NEMmRNAs.
  • To investigate the role of LARP4, a La RBP family member, in mitochondrial regulation.

Main Methods:

  • Systematic analysis of RNA targets for 150 RBPs.
  • Quantitative proteomics to assess protein levels upon LARP4 depletion.
  • Assessment of mitochondrial function following LARP4 manipulation.

Main Results:

  • LARP4 preferentially binds NEMmRNAs encoding respiratory chain complex proteins (RCCPs) and mitochondrial ribosome proteins (MRPs).
  • LARP4 depletion significantly reduces RCCP and MRP protein levels and impairs mitochondrial function.
  • LARP4 re-expression rescues the observed mitochondrial dysfunction.

Conclusions:

  • LARP4 is a novel RBP that positively regulates NEMmRNAs.
  • LARP4 is essential for maintaining mitochondrial respiratory function.
  • LARP4 plays a key role in mitochondrial homeostasis by controlling the expression of key mitochondrial proteins.
Keywords:
La module proteinRNA-binding proteineCLIPmitochondriatranslation

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