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PIN and CCCH Zn-finger domains coordinate RNA targeting in ZC3H12 family endoribonucleases

The CCCH-type zinc finger (ZnF) containing ZC3H12 ribonucleases are crucial in post-transcriptional immune homoeostasis with ZC3H12A being the only structurally studied member of the family. In this study, we present a structural-biochemical characterization of ZC3H12C, which is linked with chronic...

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Autores principales: Garg, Ankur, Roske, Yvette, Yamada, Shinnosuke, Uehata, Takuya, Takeuchi, Osamu, Heinemann, Udo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136824/
https://www.ncbi.nlm.nih.gov/pubmed/33950203
http://dx.doi.org/10.1093/nar/gkab316
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author Garg, Ankur
Roske, Yvette
Yamada, Shinnosuke
Uehata, Takuya
Takeuchi, Osamu
Heinemann, Udo
author_facet Garg, Ankur
Roske, Yvette
Yamada, Shinnosuke
Uehata, Takuya
Takeuchi, Osamu
Heinemann, Udo
author_sort Garg, Ankur
collection PubMed
description The CCCH-type zinc finger (ZnF) containing ZC3H12 ribonucleases are crucial in post-transcriptional immune homoeostasis with ZC3H12A being the only structurally studied member of the family. In this study, we present a structural-biochemical characterization of ZC3H12C, which is linked with chronic immune disorders like psoriasis. We established that the RNA substrate is cooperatively recognized by the PIN and ZnF domains of ZC3H12C and analyzed the crystal structure of ZC3H12C bound to a single-stranded RNA substrate. The RNA engages in hydrogen-bonded contacts and stacking interactions with the PIN and ZnF domains simultaneously. The ZC3H12 ZnF shows unprecedented structural features not previously observed in any member of the CCCH-ZnF family and utilizes stacking interactions via a unique combination of spatially conserved aromatic residues to align the target transcript in a bent conformation onto the ZnF scaffold. Further comparative structural analysis of ZC3H12 CCCH-ZnF suggests that a trinucleotide sequence is recognized by ZC3H12 ZnF in target RNA. Our work not only describes the initial structure-biochemical study on ZC3H12C, but also provides the first molecular insight into RNA recognition by a ZC3H12 family member. Finally, our work points to an evolutionary code for RNA recognition adopted by CCCH-type ZnF proteins.
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spelling pubmed-81368242021-05-25 PIN and CCCH Zn-finger domains coordinate RNA targeting in ZC3H12 family endoribonucleases Garg, Ankur Roske, Yvette Yamada, Shinnosuke Uehata, Takuya Takeuchi, Osamu Heinemann, Udo Nucleic Acids Res Structural Biology The CCCH-type zinc finger (ZnF) containing ZC3H12 ribonucleases are crucial in post-transcriptional immune homoeostasis with ZC3H12A being the only structurally studied member of the family. In this study, we present a structural-biochemical characterization of ZC3H12C, which is linked with chronic immune disorders like psoriasis. We established that the RNA substrate is cooperatively recognized by the PIN and ZnF domains of ZC3H12C and analyzed the crystal structure of ZC3H12C bound to a single-stranded RNA substrate. The RNA engages in hydrogen-bonded contacts and stacking interactions with the PIN and ZnF domains simultaneously. The ZC3H12 ZnF shows unprecedented structural features not previously observed in any member of the CCCH-ZnF family and utilizes stacking interactions via a unique combination of spatially conserved aromatic residues to align the target transcript in a bent conformation onto the ZnF scaffold. Further comparative structural analysis of ZC3H12 CCCH-ZnF suggests that a trinucleotide sequence is recognized by ZC3H12 ZnF in target RNA. Our work not only describes the initial structure-biochemical study on ZC3H12C, but also provides the first molecular insight into RNA recognition by a ZC3H12 family member. Finally, our work points to an evolutionary code for RNA recognition adopted by CCCH-type ZnF proteins. Oxford University Press 2021-05-05 /pmc/articles/PMC8136824/ /pubmed/33950203 http://dx.doi.org/10.1093/nar/gkab316 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Structural Biology
Garg, Ankur
Roske, Yvette
Yamada, Shinnosuke
Uehata, Takuya
Takeuchi, Osamu
Heinemann, Udo
PIN and CCCH Zn-finger domains coordinate RNA targeting in ZC3H12 family endoribonucleases
title PIN and CCCH Zn-finger domains coordinate RNA targeting in ZC3H12 family endoribonucleases
title_full PIN and CCCH Zn-finger domains coordinate RNA targeting in ZC3H12 family endoribonucleases
title_fullStr PIN and CCCH Zn-finger domains coordinate RNA targeting in ZC3H12 family endoribonucleases
title_full_unstemmed PIN and CCCH Zn-finger domains coordinate RNA targeting in ZC3H12 family endoribonucleases
title_short PIN and CCCH Zn-finger domains coordinate RNA targeting in ZC3H12 family endoribonucleases
title_sort pin and ccch zn-finger domains coordinate rna targeting in zc3h12 family endoribonucleases
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136824/
https://www.ncbi.nlm.nih.gov/pubmed/33950203
http://dx.doi.org/10.1093/nar/gkab316
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