The oxidoreductase PYROXD1 uses NAD(P)+ as an antioxidant to sustain tRNA ligase activity in pre-tRNA splicing and unfolded protein response
Аутори
Asanović, IgorStrandback, Emilia
Kroupova, Alena
Pasajlić, Đurđa
Meinhart, Anton
Tsung-Pin, Pai
Đoković, Nemanja
Anrather, Dorothea
Schuetz, Thomas
Suskiewicz, Marcin Jozef
Sillamaa, Sirelin
Kocher, Thomas
Beveridge, Rebecca
Nikolić, Katarina
Schleiffer, Alexander
Jinek, Martin
Hartl, Markus
Clausen, Tim
Penninger, Josef
Macheroux, Peter
Weitzer, Stefan
Martinez, Javier
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 b...y the flavoprotein
PYROXD1 through an unexpected redox mechanism.
Кључне речи:
PYROXD1 / oxidoreductase / myopathy / tRNA ligase complex / RtcB / oxidative stress / metalloenzyme / copper / NADPH / NADH / UPR / pre-tRNA splicingИзвор:
Molecular Cell, 2021, 81, 12, 2520-2532Издавач:
- Elsevier
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
DOI: 10.1016/j.molcel.2021.04.007
ISSN: 1097-2765
WoS: 000674490700006
Scopus: 2-s2.0-85107908607
Институција/група
PharmacyTY - JOUR AU - Asanović, Igor AU - Strandback, Emilia AU - Kroupova, Alena AU - Pasajlić, Đurđa AU - Meinhart, Anton AU - Tsung-Pin, Pai AU - Đoković, Nemanja AU - Anrather, Dorothea AU - Schuetz, Thomas AU - Suskiewicz, Marcin Jozef AU - Sillamaa, Sirelin AU - Kocher, Thomas AU - Beveridge, Rebecca AU - Nikolić, Katarina AU - Schleiffer, Alexander AU - Jinek, Martin AU - Hartl, Markus AU - Clausen, Tim AU - Penninger, Josef AU - Macheroux, Peter AU - Weitzer, Stefan AU - Martinez, Javier PY - 2021 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4905 AB - 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. PB - Elsevier T2 - Molecular Cell T1 - The oxidoreductase PYROXD1 uses NAD(P)+ as an antioxidant to sustain tRNA ligase activity in pre-tRNA splicing and unfolded protein response VL - 81 IS - 12 SP - 2520 EP - 2532 DO - 10.1016/j.molcel.2021.04.007 ER -
@article{ author = "Asanović, Igor and Strandback, Emilia and Kroupova, Alena and Pasajlić, Đurđa and Meinhart, Anton and Tsung-Pin, Pai and Đoković, Nemanja and Anrather, Dorothea and Schuetz, Thomas and Suskiewicz, Marcin Jozef and Sillamaa, Sirelin and Kocher, Thomas and Beveridge, Rebecca and Nikolić, Katarina and Schleiffer, Alexander and Jinek, Martin and Hartl, Markus and Clausen, Tim and Penninger, Josef and Macheroux, Peter and Weitzer, Stefan and Martinez, Javier", year = "2021", 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.", publisher = "Elsevier", journal = "Molecular Cell", title = "The oxidoreductase PYROXD1 uses NAD(P)+ as an antioxidant to sustain tRNA ligase activity in pre-tRNA splicing and unfolded protein response", volume = "81", number = "12", pages = "2520-2532", doi = "10.1016/j.molcel.2021.04.007" }
Asanović, I., Strandback, E., Kroupova, A., Pasajlić, Đ., Meinhart, A., Tsung-Pin, P., Đoković, N., Anrather, D., Schuetz, T., Suskiewicz, M. J., Sillamaa, S., Kocher, T., Beveridge, R., Nikolić, K., Schleiffer, A., Jinek, M., Hartl, M., Clausen, T., Penninger, J., Macheroux, P., Weitzer, S.,& Martinez, J.. (2021). The oxidoreductase PYROXD1 uses NAD(P)+ as an antioxidant to sustain tRNA ligase activity in pre-tRNA splicing and unfolded protein response. in Molecular Cell Elsevier., 81(12), 2520-2532. https://doi.org/10.1016/j.molcel.2021.04.007
Asanović I, Strandback E, Kroupova A, Pasajlić Đ, Meinhart A, Tsung-Pin P, Đoković N, Anrather D, Schuetz T, Suskiewicz MJ, Sillamaa S, Kocher T, Beveridge R, Nikolić K, Schleiffer A, Jinek M, Hartl M, Clausen T, Penninger J, Macheroux P, Weitzer S, Martinez J. The oxidoreductase PYROXD1 uses NAD(P)+ as an antioxidant to sustain tRNA ligase activity in pre-tRNA splicing and unfolded protein response. in Molecular Cell. 2021;81(12):2520-2532. doi:10.1016/j.molcel.2021.04.007 .
Asanović, Igor, Strandback, Emilia, Kroupova, Alena, Pasajlić, Đurđa, Meinhart, Anton, Tsung-Pin, Pai, Đoković, Nemanja, Anrather, Dorothea, Schuetz, Thomas, Suskiewicz, Marcin Jozef, Sillamaa, Sirelin, Kocher, Thomas, Beveridge, Rebecca, Nikolić, Katarina, Schleiffer, Alexander, Jinek, Martin, Hartl, Markus, Clausen, Tim, Penninger, Josef, Macheroux, Peter, Weitzer, Stefan, Martinez, Javier, "The oxidoreductase PYROXD1 uses NAD(P)+ as an antioxidant to sustain tRNA ligase activity in pre-tRNA splicing and unfolded protein response" in Molecular Cell, 81, no. 12 (2021):2520-2532, https://doi.org/10.1016/j.molcel.2021.04.007 . .