Structural basis for Tpt1-catalyzed 2′-PO(4) transfer from RNA and NADP(H) to NAD(+) Journal Article
| Authors: | Jacewicz, A.; Dantuluri, S.; Shuman, S. |
| Article Title: | Structural basis for Tpt1-catalyzed 2′-PO(4) transfer from RNA and NADP(H) to NAD(+) |
| Abstract: | Tpt1 is an essential agent of fungal and plant tRNA splicing that removes an internal RNA 2′-phosphate generated by tRNA ligase. Tpt1 also removes the 2′-phosphouridine mark installed by Ark1 kinase in the V-loop of archaeal tRNAs. Tpt1 performs a two-step reaction in which the 2′-PO4 attacks NAD+ to form an RNA-2′-phospho-(ADP-ribose) intermediate, and transesterification of the ADP-ribose O2′′ to the RNA 2′-phosphodiester yields 2′-OH RNA and ADP-ribose-1′′,2′′-cyclic phosphate. Here, we present structures of archaeal Tpt1 enzymes, captured as product complexes with ADP-ribose-1′′-PO4, ADP-ribose-2′′-PO4, and 2′-OH RNA, and as substrate complexes with 2′,5′-ADP and NAD+, that illuminate 2′-PO4 junction recognition and catalysis. We show that archaeal Tpt1 enzymes can use the 2′-PO4-containing metabolites NADP+ and NADPH as substrates for 2′-PO4 transfer to NAD+. A role in 2′-phospho-NADP(H) dynamics provides a rationale for the prevalence of Tpt1 in taxa that lack a capacity for internal RNA 2′-phosphorylation. Copyright © 2023 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). |
| Keywords: | controlled study; nonhuman; genetic analysis; prevalence; in vivo study; rna; transfer rna; rna, transfer; crystallization; structure analysis; dynamics; phosphate; phosphates; aspergillus fumigatus; candida albicans; nad; pyrococcus horikoshii; nicotinamide adenine dinucleotide; nadp; nicotinamide adenine dinucleotide phosphate; biochemical analysis; adenosine diphosphate ribose; aeropyrum pernix; human; article; translationally controlled tumor protein; coccidioides immitis |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 120 |
| Issue: | 44 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2023-10-31 |
| Start Page: | e2312999120 |
| Language: | English |
| DOI: | 10.1073/pnas.2312999120 |
| PUBMED: | 37883434 |
| PROVIDER: | scopus |
| PMCID: | PMC10622864 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Stewart Shuman -- Source: Scopus |
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