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Zc3h13 Regulates Nuclear RNA m6A Methylation and Mouse Embryonic Stem Cell Self-Renewal

Open access
Wen, Jing, Lv, Ruitu, Ma, Honghui, Shen, Hongjie, He, Chenxi, Wang, Jiahua, Jiao, Fangfang, Liu, Hang, Yang, Pengyuan, Tan, Li, Lan, Fei, Shi, Yujiang Geno, He, Chuan, Shi, Yang, Diao, Jianbo·2018·Molecular Cell
DOI 10.1016/j.molcel.2018.02.015
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Abstract

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.

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Metadata

Authors
Wen, J., Lv, R., Ma, H., Shen, H., He, C., Wang, J., Jiao, F., Liu, H., Yang, P., Tan, L., Lan, F., Shi, Y. G., He, C., Shi, Y., & Diao, J.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2018-03
Volume
69
Issue
6
Pages
1028-1038.e6
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2018.02.015
OpenAlex
W2791790309
Cited by
941
References
14
FWCI
28.96
Type
journal article
Language
en
Open access
bronze
Licence
Funders
  • National Key Research and Development Program of China (2016YFA0101800)
  • China “Thousand Youth Talents” (KHH1340001)
  • NSFC (91419306)
  • “973” State Key Development Program (2014CB943103)
  • ISTC (2014DFB30020)
  • Shanghai Pujiang Program (10PJ1400400)
  • NIH (R01 HG008688)

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CoChat. (2026). Citation check: Zc3h13 Regulates Nuclear RNA m6A Methylation and Mouse Embryonic Stem Cell Self-Renewal. https://app.cochat.ai/papers/10.1016/j.molcel.2018.02.015
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Wen, J., Lv, R., Ma, H., Shen, H., He, C., Wang, J., Jiao, F., Liu, H., Yang, P., Tan, L., Lan, F., Shi, Y. G., He, C., Shi, Y., & Diao, J. (2018). Zc3h13 Regulates Nuclear RNA m6A Methylation and Mouse Embryonic Stem Cell Self-Renewal. Molecular Cell. https://doi.org/10.1016/j.molcel.2018.02.015

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