Translational regulation of Chk1 expression by eIF3a via interaction with the RNA-binding protein HuR.
Translational regulation of Chk1 expression by eIF3a via interaction with the RNA-binding protein HuR.
复制标题
DOI：
10.1042/bcj20200025
复制
发表时间：
2020-05-29
期刊：
影响因子：
--
通讯作者：
Zhang JT
中科院分区：
文献类型：
--
作者：
Dong Z;Liu J;Zhang JT
eIF3a被认为是真核生物翻译起始因子3复合体的一个亚基。越来越多的证据表明，eIF3a可能通过抑制mrna亚群的翻译而加速其他mrna的翻译而具有翻译调节功能。尽管抑制mRNA翻译可能源于eIF3a与靶mRNA的5 ' - utr结合，但eIF3a如何加速mRNA翻译仍不清楚。在本研究中，我们发现eIF3a通过与直接结合Chk1 mRNA的3 ' -UTR的HuR相互作用上调Chk1而不是Chk2 mRNA的翻译。eIF3a与HuR的相互作用发生在eIF3a的10个氨基酸重复结构域和HuR的RNA识别基序结构域。这种相互作用可以有效地循环Chk1 mRNA，形成一个端到端的复合物，最近被认为可以加速mRNA的翻译。结合先前的研究结果，我们得出结论，eIF3a可能通过直接结合5 ' -UTR抑制mRNA翻译或通过与3 ' -UTR上的rna结合蛋白相互作用来加速mRNA翻译。
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.