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Updated: Jun 17, 2025
09:33
Rapid Isolation of the Mitoribosome from HEK Cells
Published on: October 4, 2018
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Structural basis of LRPPRC-SLIRP-dependent translation by the mitoribosome
Vivek Singh1, J Conor Moran2, Yuzuru Itoh3,4
1Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden.
Nature Structural & Molecular Biology
|August 12, 2024
Summary
Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) acts as an mRNA delivery factor in mitochondria. The LRPPRC-SLIRP complex regulates mitochondrial gene expression by modulating mRNA translation.
Area of Science:
- Mitochondrial biology
- Molecular genetics
- Structural biology
Background:
- Mitochondrial mRNAs require stabilization for proper function.
- Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) is a known factor for mRNA stabilization in mammalian mitochondria.
Purpose of the Study:
- To characterize LRPPRC as an mRNA delivery factor.
- To determine the structural basis of LRPPRC-SLIRP complex formation with mRNA and the mitoribosome.
- To investigate the transcript-specific effects of LRPPRC on mitochondrial mRNA translation.
Main Methods:
- Cryo-electron microscopy to determine the structure of the LRPPRC-SLIRP-mRNA-mitoribosome complex.
- RNA sequencing, metabolic labeling, and mitoribosome profiling to assess mRNA translation efficiency.
Main Results:
- The cryo-EM structure reveals LRPPRC association with mitoribosomal proteins, forming a corridor for mRNA handoff.
- SRA stem-loop-interacting RNA-binding protein (SLIRP) binds mRNA and stabilizes LRPPRC.
- LRPPRC influences mitochondrial mRNA translation efficiency in a transcript-specific manner, notably affecting cytochrome c oxidase subunits 1 and 2.
Conclusions:
- LRPPRC-SLIRP functions as an mRNA delivery factor, recruiting mitochondrial mRNAs to modulate their translation.
- The LRPPRC-SLIRP complex is a key regulator of the mitochondrial gene expression system.
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