LRPPRC-mediated folding of the mitochondrial transcriptome

Nat Commun. 2017 Nov 16;8(1):1532. doi: 10.1038/s41467-017-01221-z.


The expression of the compact mammalian mitochondrial genome requires transcription, RNA processing, translation and RNA decay, much like the more complex chromosomal systems, and here we use it as a model system to understand the fundamental aspects of gene expression. Here we combine RNase footprinting with PAR-CLIP at unprecedented depth to reveal the importance of RNA-protein interactions in dictating RNA folding within the mitochondrial transcriptome. We show that LRPPRC, in complex with its protein partner SLIRP, binds throughout the mitochondrial transcriptome, with a preference for mRNAs, and its loss affects the entire secondary structure and stability of the transcriptome. We demonstrate that the LRPPRC-SLIRP complex is a global RNA chaperone that stabilizes RNA structures to expose the required sites for translation, stabilization, and polyadenylation. Our findings reveal a general mechanism where extensive RNA-protein interactions ensure that RNA is accessible for its biological functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Fibroblasts
  • Genome, Mitochondrial / physiology
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / physiology*
  • Molecular Chaperones / physiology
  • Neoplasm Proteins / physiology*
  • Polyadenylation / physiology
  • Protein Binding / physiology
  • Protein Biosynthesis / physiology
  • Protein Footprinting / methods
  • RNA Folding / physiology*
  • RNA Stability / physiology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / physiology*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Analysis, RNA / methods
  • Transcriptome / physiology*


  • LRPPRC protein, human
  • Lrpprc protein, mouse
  • Molecular Chaperones
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Recombinant Proteins
  • SLIRP protein, human
  • SLIRP protein, mouse