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

August 13, 2018

Title

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

Author

Zbigniew Pietras, Magdalena A. Wojcik, Lukasz S. Borowski, Maciej Szewczyk, Tomasz M. Kulinski, Dominik Cysewski, Piotr P. Stepien, Andrzej Dziembowski, Roman J. Szczesny

Year

2018

Journal

Nature Communications

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.

Instrument

J-810

Keywords

Circular dichroism, RNA structure, Thermal stability, Biochemistry