A variant of guanidine-IV riboswitches exhibits evidence of a distinct ligand specificity

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2023
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European Union (EU): 681777
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RiboDisc - Discovery of novel orphan riboswitch ligands
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RNA Biology. Taylor & Francis. 2023, 20(1), pp. 10-19. ISSN 1547-6286. eISSN 1555-8584. Available under: doi: 10.1080/15476286.2022.2160562
Zusammenfassung

Riboswitches are regulatory RNAs that specifically bind a small molecule or ion. Like metabolite-binding proteins, riboswitches can evolve new ligand specificities, and some examples of this phenomenon have been validated. As part of work based on comparative genomics to discover novel riboswitches, we encountered a candidate riboswitch with striking similarities to the recently identified guanidine-IV riboswitch. This candidate riboswitch, the Gd4v motif, is predicted in four distinct bacterial phyla, thus almost as widespread as the guanidine-IV riboswitch. Bioinformatic and experimental analysis suggest that the Gd4v motif is a riboswitch that binds a ligand other than guanidine. It is found associated with gene classes that differ from genes regulated by confirmed guanidine riboswitches. In inline-probing assays, we showed that free guanidine binds only weakly to one of the tested sequences of the variant. Further tested compounds did not show binding, attenuation of transcription termination, or activation of a genetic reporter construct. We characterized an N-acetyltransferase frequently associated with the Gd4v motif and compared its substrate preference to an N-acetyltransferase that occurs under control of guanidine-IV riboswitches. The substrates of this Gd4v-motif-associated enzyme did not show activity for Gd4v RNA binding or transcription termination. Hence, the ligand of the candidate riboswitch motif remains unidentified. The variant RNA motif is predominantly found in gut metagenome sequences, hinting at a ligand that is highly relevant in this environment. This finding is a first step to determining the identity of this unknown ligand, and understanding how guanidine-IV-riboswitch-like structures can evolve to bind different ligands.

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570 Biowissenschaften, Biologie
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Variant riboswitch, guanidine, guanidinium, comparative genomics, metagenome analysis, N-acetyltransferase, GNAT, agmatine, arginine
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ISO 690LENKEIT, Felina, Iris ECKERT, Malte SINN, Franziskus HAUTH, Jörg S. HARTIG, Zasha WEINBERG, 2023. A variant of guanidine-IV riboswitches exhibits evidence of a distinct ligand specificity. In: RNA Biology. Taylor & Francis. 2023, 20(1), pp. 10-19. ISSN 1547-6286. eISSN 1555-8584. Available under: doi: 10.1080/15476286.2022.2160562
BibTex
@article{Lenkeit2023varia-66212,
  year={2023},
  doi={10.1080/15476286.2022.2160562},
  title={A variant of guanidine-IV riboswitches exhibits evidence of a distinct ligand specificity},
  number={1},
  volume={20},
  issn={1547-6286},
  journal={RNA Biology},
  pages={10--19},
  author={Lenkeit, Felina and Eckert, Iris and Sinn, Malte and Hauth, Franziskus and Hartig, Jörg S. and Weinberg, Zasha}
}
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