eIF3a is a putative subunit of the eukaryotic translation initiation factor 3 complex. Accumulating evidence suggests that eIF3a may have a translational regulatory function by suppressing translation of a subset of mRNAs while accelerating that of other mRNAs. Albeit the suppression of mRNA translation may derive from eIF3a binding to the 5′-UTRs of target mRNAs, how eIF3a may accelerate mRNA translation remains unknown. In this study, we show that eIF3a up-regulates translation of Chk1 but not Chk2 mRNA by interacting with HuR, which binds directly to the 3′-UTR of Chk1 mRNA. The interaction between eIF3a and HuR occurs at the 10-amino-acid repeat domain of eIF3a and the RNA recognition motif domain of HuR. This interaction may effectively circularize Chk1 mRNA to form an end-to-end complex that has recently been suggested to accelerate mRNA translation. Together with previous findings, we conclude that eIF3a may regulate mRNA translation by directly binding to the 5′-UTR to suppress or by interacting with RNA-binding proteins at 3′-UTRs to accelerate mRNA translation.
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May 2020
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The cover image shows high resolution of the 20 lowest energy structures of kringle 2 of human plasminogen to AGL55-NS88.2 (top) and KT155-SS1448 (bottom). To learn more about this, see the article by Qiu and colleagues (pp. 1613–1630). The image was provided by Francis J. Castellino.
Research Article|
May 29 2020
Translational regulation of Chk1 expression by eIF3a via interaction with the RNA-binding protein HuR
Zizheng Dong;
Zizheng Dong
Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, U.S.A.
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Jianguo Liu;
Jianguo Liu
Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, U.S.A.
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Jian-Ting Zhang
Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, U.S.A.
Correspondence: Jian-Ting Zhang (JianTing.Zhang@UToledo.Edu)
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Publisher: Portland Press Ltd
Received:
January 09 2020
Revision Received:
May 04 2020
Accepted:
May 07 2020
Accepted Manuscript online:
May 11 2020
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem J (2020) 477 (10): 1939–1950.
Article history
Received:
January 09 2020
Revision Received:
May 04 2020
Accepted:
May 07 2020
Accepted Manuscript online:
May 11 2020
Citation
Zizheng Dong, Jianguo Liu, Jian-Ting Zhang; Translational regulation of Chk1 expression by eIF3a via interaction with the RNA-binding protein HuR. Biochem J 29 May 2020; 477 (10): 1939–1950. doi: https://doi.org/10.1042/BCJ20200025
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