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The oxidoreductase PYROXD1 uses NAD(P)+ as an antioxidant to sustain tRNA ligase activity in pre-tRNA splicing and unfolded protein response
dc.creator | Asanović, Igor | |
dc.creator | Strandback, Emilia | |
dc.creator | Kroupova, Alena | |
dc.creator | Pasajlić, Đurđa | |
dc.creator | Meinhart, Anton | |
dc.creator | Tsung-Pin, Pai | |
dc.creator | Đoković, Nemanja | |
dc.creator | Anrather, Dorothea | |
dc.creator | Schuetz, Thomas | |
dc.creator | Suskiewicz, Marcin Jozef | |
dc.creator | Sillamaa, Sirelin | |
dc.creator | Kocher, Thomas | |
dc.creator | Beveridge, Rebecca | |
dc.creator | Nikolić, Katarina | |
dc.creator | Schleiffer, Alexander | |
dc.creator | Jinek, Martin | |
dc.creator | Hartl, Markus | |
dc.creator | Clausen, Tim | |
dc.creator | Penninger, Josef | |
dc.creator | Macheroux, Peter | |
dc.creator | Weitzer, Stefan | |
dc.creator | Martinez, Javier | |
dc.date.accessioned | 2023-07-07T12:31:57Z | |
dc.date.available | 2023-07-07T12:31:57Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 1097-2765 | |
dc.identifier.uri | https://farfar.pharmacy.bg.ac.rs/handle/123456789/4905 | |
dc.description.abstract | The tRNA ligase complex (tRNA-LC) splices precursor tRNAs (pre-tRNA), and Xbp1-mRNA during the unfolded protein response (UPR). In aerobic conditions, a cysteine residue bound to two metal ions in its ancient, catalytic subunit RTCB could make the tRNA-LC susceptible to oxidative inactivation. Here, we confirm this hypothesis and reveal a co-evolutionary association between the tRNA-LC and PYROXD1, a conserved and essential oxidoreductase. We reveal that PYROXD1 preserves the activity of the mammalian tRNA-LC in pre-tRNA splicing and UPR. PYROXD1 binds the tRNA-LC in the presence of NAD(P)H and converts RTCB-bound NAD(P)H into NAD(P)+, a typical oxidative co-enzyme. However, NAD(P)+ here acts as an antioxidant and protects the tRNA-LC from oxidative inactivation, which is dependent on copper ions. Genetic variants of PYROXD1 that cause human myopathies only partially support tRNA-LC activity. Thus, we establish the tRNA-LC as an oxidation-sensitive metalloenzyme, safeguarded by the flavoprotein PYROXD1 through an unexpected redox mechanism. | sr |
dc.language.iso | en | sr |
dc.publisher | Elsevier | sr |
dc.relation | info:eu-repo/grantAgreement/MESTD/inst-2020/200161/RS// | sr |
dc.rights | openAccess | sr |
dc.source | Molecular Cell | sr |
dc.subject | PYROXD1 | sr |
dc.subject | oxidoreductase | sr |
dc.subject | myopathy | sr |
dc.subject | tRNA ligase complex | sr |
dc.subject | RtcB | sr |
dc.subject | oxidative stress | sr |
dc.subject | metalloenzyme | sr |
dc.subject | copper | sr |
dc.subject | NADPH | sr |
dc.subject | NADH | sr |
dc.subject | UPR | sr |
dc.subject | pre-tRNA splicing | sr |
dc.title | The oxidoreductase PYROXD1 uses NAD(P)+ as an antioxidant to sustain tRNA ligase activity in pre-tRNA splicing and unfolded protein response | sr |
dc.type | article | sr |
dc.rights.license | ARR | sr |
dc.citation.volume | 81 | |
dc.citation.issue | 12 | |
dc.citation.spage | 2520 | |
dc.citation.epage | 2532 | |
dc.citation.rank | aM21 | |
dc.identifier.wos | 000674490700006 | |
dc.identifier.doi | 10.1016/j.molcel.2021.04.007 | |
dc.identifier.scopus | 2-s2.0-85107908607 | |
dc.identifier.fulltext | http://farfar.pharmacy.bg.ac.rs/bitstream/id/13426/The_oxidoreductase_PYROXD1_pub_2021.pdf | |
dc.type.version | publishedVersion | sr |