Zc3h13 regulates nuclear RNA m6A methylation and mouse embryonic stem cell self-renewal

By Jing Wen, Ruitu Lv, Honghui Ma, Hongjie Shen, Chenxi He, Jiahua Wang, Fangfang Jiao, Hang Liu, Pengyuan Yang, Li Tan and 5 more. Molecules and Cells, 2018

790 citations recorded by the source corpus.

Summary N6-methyladenosine (m6A) is an abundant modification in eukaryotic mRNA, regulating mRNA dynamics by influencing mRNA stability, splicing, export and translation. However, the precise m6A regulating machinery still remains incompletely understood. Here we demonstrate that ZC3H13, a zinc finger protein, plays an important role in modulating RNA m6A methylation in the nucleus. We show that knockdown of Zc3h13 in mouse embryonic stem cell significantly decreases global m6A level on mRNA. Upon Zc3h13 knockdown a great majority of WTAP, Virilizer and Hakai translocate to the cytoplasm, suggesting that Zc3h13 is required for nuclear localization of the Zc3h13-WTAP-Virilizer-Hakai complex, which is important for RNA m6A methylation. Finally, Zc3h13 depletion, as does WTAP, Virilizer or Hakai, impairs self-renewal and triggers mESC differentiation. Taken together, our findings demonstrate that Zc3h13 plays a critical role in anchoring WTAP, Virilizer and Hakai in the nucleus to facilitate m6A methylation and to regulate mESC self-renewal.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/366cf83938633e216aec53dfc59dd22b48fc4e4c

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In Molecular Biology

1. Chuan He
2. Hailing Shi
3. Jiangbo W
4. Phillip J Hsu
5. Ying Yang
6. Yu-Sheng Chen
7. Yun-Gui Yang
8. Samie R. Jaffrey

Citations in the corpus

• Where, when and how: context-dependent functions of RNA methylation writers, readers, and erasers (2019, background): “…specifically to the 3’UTR (Yue et al., 2018); Zinc finger CCCH-type containing 13 (ZC3H13) facilitates nuclear localization of the writer complex (Wen et al., 2018); and RNA binding motif protein 15/15B (RBM15/15B) is reported to bind U-riched regions and may facilitate methylation of certain…”
• m6A RNA methylation: from mechanisms to therapeutic potential (2021, neutral): “:3) u (cid:4) zi (cid:4) cka et al , 2017; Guo et al , 2018; ; Wen et al , 2018; Yue et al , 2018).”
• Methylation multiplicity and its clinical values in cancer (2021, neutral): “25).”
• Functions of N6-methyladenosine and its role in cancer (2019, background): “* Correspondence: gangyin@csu.edu.cn 1Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha 410008, Hunan Province, China Full list of author information is available at the end of the article ZC3H13 enhances m6A through bridging WTAP to the ”
• Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism (2018, background): “revealed that mouse Zc3h13 is required for nuclear localization of the Zc3h13-WTAP-VirilizerHakai complex and regulates mouse embryonic stem cell (ESC) self-renewal through facilitating m(6)A methylation.(58) Knuckles et al.”