Characterization of a novel eukaryal nick-sealing RNA ligase from Naegleria gruberi

RNA
Mihaela-Carmen Unciuleac, Stewart Shuman

Abstract

The proteome of the amoebo-flagellate protozoan Naegleria gruberi is rich in candidate RNA repair enzymes, including 15 putative RNA ligases, one of which, NgrRnl, is a eukaryal homolog of Deinococcus radiodurans RNA ligase, DraRnl. Here we report that purified recombinant NgrRnl seals nicked 3'-OH/5'-PO4 duplexes in which the 3'-OH strand is RNA. It does so via the "classic" ligase pathway, entailing reaction with ATP to form a covalent NgrRnl-AMP intermediate, transfer of AMP to the nick 5'-PO4, and attack of the RNA 3'-OH on the adenylylated nick to form a 3'-5' phosphodiester. Unlike members of the four known families of ATP-dependent RNA ligases, NgrRnl lacks a carboxy-terminal appendage to its nucleotidyltransferase domain. Instead, it contains a defining amino-terminal domain that we show is important for 3'-OH/5'-PO4 nick-sealing and ligase adenylylation, but dispensable for phosphodiester synthesis at a preadenylylated nick. We propose that NgrRnl, DraRnl, and their homologs from diverse bacteria, viruses, and unicellular eukarya comprise a new "Rnl5 family" of nick-sealing ligases with a signature domain organization.

References

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Aug 31, 2004·The Journal of Biological Chemistry·Alexandra Martins, Stewart Shuman
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Nov 5, 2014·EMBO Reports·Sara Guckian KosmaczewskiMarc Hammarlund

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Citations

Oct 30, 2015·Proceedings of the National Academy of Sciences of the United States of America·Mihaela-Carmen UnciuleacStewart Shuman
Aug 19, 2016·Nucleic Acids Research·A Maxwell Burroughs, L Aravind
Feb 23, 2017·Proceedings of the National Academy of Sciences of the United States of America·Mihaela-Carmen UnciuleacStewart Shuman
Jul 28, 2018·Frontiers in Cellular and Infection Microbiology·Elisa Azuara-LiceagaLuis G Brieba
Jun 19, 2019·Biochimie·Hubert F BeckerHannu Myllykallio

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