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 (May 2021) PIN and CCCH Zn-finger domains coordinate RNA targeting in ZC3H12 family endoribonucleases. Nucleic Acids Research, 49 (9). pp. 5369-5381. ISSN 0305-1048

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Abstract

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.

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > analysis and processing bioinformatics bioinformatics > genomics and proteomics > analysis and processing > DNA RNA Processing bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics Investigative techniques and equipment bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal organism description > animal > mammal organism description > animal > mammal > rodent > mouse bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > ribonuclease organism description > animal > mammal > rodent Investigative techniques and equipment > x ray crystallography bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > zinc finger proteins
CSHL Authors:	Garg, Ankur
Communities:	CSHL labs > Joshua-Tor lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	21 May 2021
Date Deposited:	24 Jun 2021 13:12
Last Modified:	23 Jan 2024 21:17
PMCID:	PMC8136824
URI:	https://repository.cshl.edu/id/eprint/40224

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