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Selective Cleavage at CCA Ends and Anticodon Loops of tRNAs by Stress-Induced RNases

Stress-induced tRNA cleavage has been implicated in various cellular processes, where tRNA fragments play diverse regulatory roles. Angiogenin (ANG), a member of the RNase A superfamily, induces cleavage of tRNAs resulting in the formation of tRNA-derived stress-induced RNAs (tiRNAs) that contribute...

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Autores principales: Akiyama, Yasutoshi, Lyons, Shawn M., Fay, Marta M., Tomioka, Yoshihisa, Abe, Takaaki, Anderson, Paul J., Ivanov, Pavel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920990/
https://www.ncbi.nlm.nih.gov/pubmed/35300117
http://dx.doi.org/10.3389/fmolb.2022.791094
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author Akiyama, Yasutoshi
Lyons, Shawn M.
Fay, Marta M.
Tomioka, Yoshihisa
Abe, Takaaki
Anderson, Paul J.
Ivanov, Pavel
author_facet Akiyama, Yasutoshi
Lyons, Shawn M.
Fay, Marta M.
Tomioka, Yoshihisa
Abe, Takaaki
Anderson, Paul J.
Ivanov, Pavel
author_sort Akiyama, Yasutoshi
collection PubMed
description Stress-induced tRNA cleavage has been implicated in various cellular processes, where tRNA fragments play diverse regulatory roles. Angiogenin (ANG), a member of the RNase A superfamily, induces cleavage of tRNAs resulting in the formation of tRNA-derived stress-induced RNAs (tiRNAs) that contribute to translational reprogramming aiming at cell survival. In addition to cleaving tRNA anticodon loops, ANG has been shown to cleave 3′-CCA termini of tRNAs in vitro, although it is not known whether this process occurs in cells. It has also been suggested that tiRNAs can be generated independently of ANG, although the role of other stress-induced RNases in tRNA cleavage is poorly understood. Using gene editing and biochemical approaches, we examined the involvement of ANG in stress-induced tRNA cleavage by focusing on its cleavage of CCA-termini as well as anticodon loops. We show that ANG is not responsible for CCA-deactivation under sodium arsenite (SA) treatment in cellulo, and although ANG treatment significantly increases 3′-tiRNA levels in cells, the majority of 3′-tiRNAs retain their 3′-CCA termini. Instead, other RNases can cleave CCA-termini in cells, although with low efficiency. Moreover, in the absence of ANG, other RNases are able to promote the production of tiRNAs in cells. Depletion of RNH1 (an endogenous inhibitor of RNase A superfamily) promotes constitutively-produced tiRNAs and CCA-deactivated tRNAs in cells. Interestingly, SA treatment in RNH1-depleted cells did not increase the amount of tiRNAs or CCA-deactivated tRNAs, suggesting that RNase A superfamily enzymes are largely responsible for SA-induced tRNA cleavage. We show that interplay between stress-induced RNases cause targeting tRNAs in a stress-specific manner in cellulo.
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spelling pubmed-89209902022-03-16 Selective Cleavage at CCA Ends and Anticodon Loops of tRNAs by Stress-Induced RNases Akiyama, Yasutoshi Lyons, Shawn M. Fay, Marta M. Tomioka, Yoshihisa Abe, Takaaki Anderson, Paul J. Ivanov, Pavel Front Mol Biosci Molecular Biosciences Stress-induced tRNA cleavage has been implicated in various cellular processes, where tRNA fragments play diverse regulatory roles. Angiogenin (ANG), a member of the RNase A superfamily, induces cleavage of tRNAs resulting in the formation of tRNA-derived stress-induced RNAs (tiRNAs) that contribute to translational reprogramming aiming at cell survival. In addition to cleaving tRNA anticodon loops, ANG has been shown to cleave 3′-CCA termini of tRNAs in vitro, although it is not known whether this process occurs in cells. It has also been suggested that tiRNAs can be generated independently of ANG, although the role of other stress-induced RNases in tRNA cleavage is poorly understood. Using gene editing and biochemical approaches, we examined the involvement of ANG in stress-induced tRNA cleavage by focusing on its cleavage of CCA-termini as well as anticodon loops. We show that ANG is not responsible for CCA-deactivation under sodium arsenite (SA) treatment in cellulo, and although ANG treatment significantly increases 3′-tiRNA levels in cells, the majority of 3′-tiRNAs retain their 3′-CCA termini. Instead, other RNases can cleave CCA-termini in cells, although with low efficiency. Moreover, in the absence of ANG, other RNases are able to promote the production of tiRNAs in cells. Depletion of RNH1 (an endogenous inhibitor of RNase A superfamily) promotes constitutively-produced tiRNAs and CCA-deactivated tRNAs in cells. Interestingly, SA treatment in RNH1-depleted cells did not increase the amount of tiRNAs or CCA-deactivated tRNAs, suggesting that RNase A superfamily enzymes are largely responsible for SA-induced tRNA cleavage. We show that interplay between stress-induced RNases cause targeting tRNAs in a stress-specific manner in cellulo. Frontiers Media S.A. 2022-03-01 /pmc/articles/PMC8920990/ /pubmed/35300117 http://dx.doi.org/10.3389/fmolb.2022.791094 Text en Copyright © 2022 Akiyama, Lyons, Fay, Tomioka, Abe, Anderson and Ivanov. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Akiyama, Yasutoshi
Lyons, Shawn M.
Fay, Marta M.
Tomioka, Yoshihisa
Abe, Takaaki
Anderson, Paul J.
Ivanov, Pavel
Selective Cleavage at CCA Ends and Anticodon Loops of tRNAs by Stress-Induced RNases
title Selective Cleavage at CCA Ends and Anticodon Loops of tRNAs by Stress-Induced RNases
title_full Selective Cleavage at CCA Ends and Anticodon Loops of tRNAs by Stress-Induced RNases
title_fullStr Selective Cleavage at CCA Ends and Anticodon Loops of tRNAs by Stress-Induced RNases
title_full_unstemmed Selective Cleavage at CCA Ends and Anticodon Loops of tRNAs by Stress-Induced RNases
title_short Selective Cleavage at CCA Ends and Anticodon Loops of tRNAs by Stress-Induced RNases
title_sort selective cleavage at cca ends and anticodon loops of trnas by stress-induced rnases
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920990/
https://www.ncbi.nlm.nih.gov/pubmed/35300117
http://dx.doi.org/10.3389/fmolb.2022.791094
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