ZC3H14 facilitates backsplicing by binding to exon-intron boundary and 3' UTR.

Autor:	Li Q; Department of Clinical Laboratory, The First Affiliated Hospital of USTC, The RNA Institute, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China (USTC), Hefei 230027, China., Yang G; Division of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China., Ren B; Department of Pulmonary and Critical Care Medicine, Regional Medical Center for National Institute of Respiratory Disease, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China., Liu X; Department of Clinical Laboratory, The First Affiliated Hospital of USTC, The RNA Institute, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China (USTC), Hefei 230027, China., Tang LQ; Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China., Shi Q; Division of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China., Shan G; Department of Clinical Laboratory, The First Affiliated Hospital of USTC, The RNA Institute, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China (USTC), Hefei 230027, China; Center for Advanced Interdisciplinary Science and Biomedicine of IHM, University of Science and Technology of China, Hefei 230071, China. Electronic address: shange@ustc.edu.cn., Wang X; Department of Clinical Laboratory, The First Affiliated Hospital of USTC, The RNA Institute, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China (USTC), Hefei 230027, China. Electronic address: wxl20089@ustc.edu.cn.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2024 Nov 21; Vol. 84 (22), pp. 4314-4333.e9. Date of Electronic Publication: 2024 Oct 25.
DOI:	10.1016/j.molcel.2024.10.001
Abstrakt:	Circular RNAs (circRNAs) are natural outputs of eukaryotic transcription and RNA processing and have emerged as critical regulators in physiology and diseases. Although multiple cis-elements and trans-factors are reported to modulate the backsplicing of circRNA biogenesis, most of these regulations play roles in flanking introns of circRNAs. Here, using a genome-wide CRISPR knockout screen, we have identified an evolutionarily conserved RNA-binding protein ZC3H14 in regulating circRNA biogenesis. ZC3H14 binds to 3' and 5' exon-intron boundaries and 3' UTRs of cognate mRNAs to promote circRNA biogenesis through dimerization and the association with spliceosome. Yeast knockout of the ZC3H14 ortholog Nab2 has significantly lower levels of circRNAs. Zc3h14 -/- mice exhibit disrupted spermatogenesis and reduced testicular circRNA levels. Additionally, expression levels of human ZC3H14 are associated with non-obstructive azoospermia. Our findings reveal a conserved requirement for ZC3H14 in the modulation of backsplicing and link ZC3H14 and circRNA biogenesis to male fertility. Competing Interests: Declaration of interests G.S., X.W., and Q.L. have an ownership interest in a patent related to this research. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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