Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-05007-9
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Funding
- National Science Centre, Poland [UMO-2014/12/W/NZ1/00463, UMO-2013/11/13/NZ1/00089, UMO-2014/13/D/NZ2/01114]
- ERC [309419]
- European Union: the European Regional Development Fund [POIG.02.02.00-14-024/08-00]
- Next Generation Sequencing Platform at the International Institute of Molecular and Cell Biology in Warsaw [6405/IA/1789/2014]
- European Research Council (ERC) [309419] Funding Source: European Research Council (ERC)
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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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