Messenger RNA delivery to mitoribosomes - hints from a bacterial toxin

FEBS J. 2021 Jan;288(2):437-451. doi: 10.1111/febs.15342. Epub 2020 May 11.

Abstract

In mammalian mitochondria, messenger RNA is processed and matured from large primary transcripts in structures known as RNA granules. The identity of the factors and process transferring the matured mRNA to the mitoribosome for translation is unclear. Nascent mature transcripts are believed to associate initially with the small mitoribosomal subunit prior to recruitment of the large subunit to form the translationally active monosome. When the small subunit fails to assemble, however, the stability of mt-mRNA is only marginally affected, and under these conditions, the LRPPRC/SLIRP RNA-binding complex has been implicated in maintaining mt-mRNA stability. Here, we exploit the activity of a bacterial ribotoxin, VapC20, to show that in the absence of the large mitoribosomal subunit, mt-mRNA species are selectively lost. Further, if the small subunit is also depleted, the mt-mRNA levels are recovered. As a consequence of these data, we suggest a natural pathway for loading processed mt-mRNA onto the mitoribosome.

Keywords: LRPPRC/SLIRP; SRL; VapC20; mitochondrial mRNA turnover; mitoribosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Toxins / genetics*
  • Bacterial Toxins / metabolism
  • Base Sequence
  • Biological Transport
  • Cell Engineering / methods
  • Cell Line
  • HEK293 Cells
  • Humans
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure
  • Mitochondrial Proton-Translocating ATPases / genetics
  • Mitochondrial Proton-Translocating ATPases / metabolism
  • Mitochondrial Ribosomes / metabolism*
  • Mitochondrial Ribosomes / ultrastructure
  • Mycobacterium tuberculosis / chemistry
  • Mycobacterium tuberculosis / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neurospora crassa / chemistry
  • Neurospora crassa / metabolism
  • Nucleic Acid Conformation
  • Protein Biosynthesis*
  • RNA Processing, Post-Transcriptional
  • RNA Stability
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA, Ribosomal, 16S / chemistry
  • RNA, Ribosomal, 16S / genetics*
  • RNA, Ribosomal, 16S / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Ribonucleases / genetics*
  • Ribonucleases / metabolism

Substances

  • Bacterial Toxins
  • LRPPRC protein, human
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Ribosomal, 16S
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • SLIRP protein, human
  • Ribonucleases
  • VapC20 protein, Mycobacterium tuberculosis
  • Mitochondrial Proton-Translocating ATPases