8tg3

Publication Abstract from PubMed

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'-PO(4) 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-PO(4), ADP-ribose-2-PO(4), and 2'-OH RNA, and as substrate complexes with 2',5'-ADP and NAD(+), that illuminate 2'-PO(4) junction recognition and catalysis. We show that archaeal Tpt1 enzymes can use the 2'-PO(4)-containing metabolites NADP(+) and NADPH as substrates for 2'-PO(4) 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.

Structural basis for Tpt1-catalyzed 2'-PO(4) transfer from RNA and NADP(H) to NAD().,Jacewicz A, Dantuluri S, Shuman S Proc Natl Acad Sci U S A. 2023 Oct 31;120(44):e2312999120. doi: , 10.1073/pnas.2312999120. Epub 2023 Oct 26. PMID:37883434^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.