Structures of RNA phosphotransferase Tpt1 reveal distinct binding modes for an RNA 2′-PO(4) splice junction versus a 5′-PO(4) mononucleotide Journal Article
| Authors: | Jacewicz, A.; Damha, M. J.; Shuman, S. |
| Article Title: | Structures of RNA phosphotransferase Tpt1 reveal distinct binding modes for an RNA 2′-PO(4) splice junction versus a 5′-PO(4) mononucleotide |
| Abstract: | Tpt1 is a widely distributed enzyme that removes an internal RNA 2 '-phosphate by transfer to NAD+, via a two-step reaction in which: (i) the RNA 2 '-PO4 attacks NAD+ to form an RNA-2 '-phospho-(ADP-ribose) intermediate and expel nicotinamide; and (ii) the ADP-ribose O2 '' attacks the RNA 2 '-phosphodiester to form 2 '-OH RNA and ADP-ribose-1 '',2 ''-cyclic phosphate products. Tpt1 can also execute a single-step ADP-ribosyltransferase reaction at a 5 '-monophosphate nucleic acid terminus that installs a 5 '-phospho-ADP-ribose cap structure. Here we present crystal structures of Tpt1 bound to an RNA containing an internal 2 '-PO4 mark (the substrate for the canonical Tpt1 pathway) and in a complex with 5 '-AMP. We find that Tpt1 has distinct binding modes, whereby the RNA 2 '-PO4 and the AMP 5 '-PO4 are engaged by the same set of active site amino acids, but the 2 '-PO4 nucleoside and the 5 '-nucleoside occupy different sites on the enzyme. |
| Keywords: | trna splicing; nicotinamide adenine dinucleotide; enzyme; saccharomyces-cerevisiae; adp-ribosylation; ligated transfer-rna; 2'-phosphotransferase; adp-ribosyl transfer |
| Journal Title: | RNA |
| Volume: | 31 |
| Issue: | 7 |
| ISSN: | 1355-8382 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2025-08-01 |
| Start Page: | 916 |
| End Page: | 922 |
| Language: | English |
| ACCESSION: | WOS:001509425000001 |
| DOI: | 10.1261/rna.080444.125 |
| PROVIDER: | wos |
| PMCID: | PMC12170183 |
| PUBMED: | 40324821 |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Stewart Shuman -- Source: Wos |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work