TY  - 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 . .