UG/Abi: a highly diverse family of prokaryotic reverse transcriptases associated with defense functions

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  • Rodríguez Mestre, Mario
  • Linyi Alex Gao
  • Shiraz A. Shah
  • Adrián López-Beltrán
  • Alejandro González-Delgado
  • Francisco Martínez-Abarca
  • Jaime Iranzo
  • Modesto Redrejo-Rodríguez
  • Feng Zhang
  • Nicolás Toro

Reverse transcriptases (RTs) are enzymes capable of synthesizing DNA using RNA as a template. Within the last few years, a burst of research has led to the discovery of novel prokaryotic RTs with diverse antiviral properties, such as DRTs (Defense-associated RTs), which belong to the so-called group of unknown RTs (UG) and are closely related to the Abortive Infection system (Abi) RTs. In this work, we performed a systematic analysis of UG and Abi RTs, increasing the number of UG/Abi members up to 42 highly diverse groups, most of which are predicted to be functionally associated with other gene(s) or domain(s). Based on this information, we classified these systems into three major classes. In addition, we reveal that most of these groups are associated with defense functions and/or mobile genetic elements, and demonstrate the antiphage role of four novel groups. Besides, we highlight the presence of one of these systems in novel families of human gut viruses infecting members of the Bacteroidetes and Firmicutes phyla. This work lays the foundation for a comprehensive and unified understanding of these highly diverse RTs with enormous biotechnological potential.

Original languageEnglish
JournalNucleic Acids Research
Volume50
Issue number11
Pages (from-to)6084-6101
Number of pages18
ISSN0305-1048
DOIs
Publication statusPublished - 24 Jun 2022

Bibliographical note

Funding Information:
MCIN/AEI/10.13039/501100011033/FEDER 'Una manera de hacer Europa' [BIO2017-82244-P to N.T]; MCIN/AEI/10.13039/501100011033 [PID2020-113207GB-I00 to N.T and F.M.A.]; M.R.M. is supported by the FPI-UAM program from Universidad Autónoma de Madrid; L.G. is supported by the Society of Fellows of Harvard University; S.A.S. is a recipient of a Novo Nordisk Foundation project grant in basic bioscience [NNF18OC0052965]; A.L.B. is a recipient of FPI fellowship [PRE2020-092935] from Spanish Ministry of Science and Innovation; J.I. is supported by the 'Ramón y Cajal' program from the Spanish Ministry of Science [RYC-2017-22524]; Agencia Estatal de Investigación of Spain [PID2019-106618GA-I00]; 'Severo Ochoa Program for Centres of Excellence in R&D' from the Agencia Estatal de Investigación of Spain [SEV-2016-0672 (2017-2021) to the C.B.G.P.]; M.R.R. is funded by grants from the Spanish Ministry of Science, Innovation and Universities [PGC2018-093723-A-100, AEI/FEDER]; Fundación Ramón Areces (VirHostOmics); F.Z. is supported by NIH [1DP1-HL141201 and 2R01HG009761-05]; Howard Hughes Medical Institute; Open Philanthropy, the Edward Mallinckrodt, Jr. Foundation; Poitras Center for Psychiatric Disorders Research at MIT; Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT; Yang-Tan Molecular Therapeutics Center at McGovern; Phillips family and J. and P. Poitras. Funding for open access charge: [PID2020-113207GB-I00] from the MCIN/AEI/10.13039/501100011033.

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

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