2. Academic Validation
  3. Dedicated surveillance mechanism controls G-quadruplex forming non-coding RNAs in human mitochondria

Dedicated surveillance mechanism controls G-quadruplex forming non-coding RNAs in human mitochondria

  • Nat Commun. 2018 Jul 2;9(1):2558. doi: 10.1038/s41467-018-05007-9.
Zbigniew Pietras 1 2,  Magdalena A Wojcik 1 3,  Lukasz S Borowski 1 3,  Maciej Szewczyk 1 3,  Tomasz M Kulinski 1,  Dominik Cysewski 1,  Piotr P Stepien 1 3,  Andrzej Dziembowski 4 5,  Roman J Szczesny 6 7
Affiliations

Affiliations

  • 1 Institute of Biochemistry and Biophysics Polish Academy of Sciences, Laboratory of RNA Biology and Functional Genomics, Pawinskiego 5A, 02-106, Warsaw, Poland.
  • 2 International Institute of Molecular and Cell Biology, Laboratory of Protein Structure, Ks. Trojdena 4, 02-109, Warsaw, Poland.
  • 3 Faculty of Biology, Institute of Genetics and Biotechnology, University of Warsaw, Pawinskiego 5A, 02-106, Warsaw, Poland.
  • 4 Institute of Biochemistry and Biophysics Polish Academy of Sciences, Laboratory of RNA Biology and Functional Genomics, Pawinskiego 5A, 02-106, Warsaw, Poland. [email protected].
  • 5 Faculty of Biology, Institute of Genetics and Biotechnology, University of Warsaw, Pawinskiego 5A, 02-106, Warsaw, Poland. [email protected].
  • 6 Institute of Biochemistry and Biophysics Polish Academy of Sciences, Laboratory of RNA Biology and Functional Genomics, Pawinskiego 5A, 02-106, Warsaw, Poland. [email protected].
  • 7 Faculty of Biology, Institute of Genetics and Biotechnology, University of Warsaw, Pawinskiego 5A, 02-106, Warsaw, Poland. [email protected].
PMID: 29967381 DOI: 10.1038/s41467-018-05007-9
Abstract

The GC skew in vertebrate mitochondrial genomes results in synthesis of RNAs that are prone to form G-quadruplexes (G4s). Such RNAs, although mostly non-coding, are transcribed at high rates and are degraded by an unknown mechanism. Here we describe a dedicated mechanism of degradation of G4-containing RNAs, which is based on cooperation between mitochondrial degradosome and quasi-RNA recognition motif (qRRM) protein GRSF1. This cooperation prevents accumulation of G4-containing transcripts in human mitochondria. In vitro reconstitution experiments show that GRSF1 promotes G4 melting that facilitates degradosome-mediated decay. Among degradosome and GRSF1 regulated transcripts we identified one that undergoes post-transcriptional modification. We show that GRSF1 proteins form a distinct qRRM group found only in vertebrates. The appearance of GRSF1 coincided with changes in the mitochondrial genome, which allows the emergence of G4-containing RNAs. We propose that GRSF1 appearance is an evolutionary adaptation enabling control of G4 RNA.

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