The RNA repair proteins RtcAB regulate transcription activator RtcR via its CRISPR-associated Rossmann fold domain
Ioly Kotta-Loizou,
Maria Grazia Giuliano,
Milija Jovanovic,
Jorrit Schaefer,
Fuzhou Ye,
Nan Zhang,
Danai Athina Irakleidi,
Xiaojiao Liu,
Xiaodong Zhang,
Martin Buck,
Christoph Engl
Affiliations
Ioly Kotta-Loizou
Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK; Corresponding author
Maria Grazia Giuliano
School of Biological and Behavioural Sciences, Queen Mary University of London, London E1 4NS, UK
Milija Jovanovic
Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK
Jorrit Schaefer
Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK
Fuzhou Ye
Section of Structural Biology, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK
Nan Zhang
Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK; Houston Methodist Research Institute, Houston, TX 77030, USA
Danai Athina Irakleidi
Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK
Xiaojiao Liu
Section of Structural Biology, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK; College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
Xiaodong Zhang
Section of Structural Biology, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK
Martin Buck
Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK
Christoph Engl
Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK; School of Biological and Behavioural Sciences, Queen Mary University of London, London E1 4NS, UK; Corresponding author
Summary: CRISPR-associated Rossmann fold (CARF) domain signaling underpins modulation of CRISPR-Cas nucleases; however, the RtcR CARF domain controls expression of two conserved RNA repair enzymes, cyclase RtcA and ligase RtcB. Here, we demonstrate that RtcAB are required for RtcR-dependent transcription activation and directly bind to RtcR CARF. RtcAB catalytic activity is not required for complex formation with CARF, but is essential yet not sufficient for RtcRAB-dependent transcription activation, implying the need for an additional RNA repair-dependent activating signal. This signal differs from oligoadenylates, a known ligand of CARF domains, and instead appears to originate from the translation apparatus: RtcB repairs a tmRNA that rescues stalled ribosomes and increases translation elongation speed. Taken together, our data provide evidence for an expanded range for CARF domain signaling, including the first evidence of its control via in trans protein-protein interactions, and a feed-forward mechanism to regulate RNA repair required for a functioning translation apparatus.
