CNOT7 outcompetes its paralog CNOT8 for integration into the CCR4-NOT complex.
CNOT7 outcompetes its paralog CNOT8 for integration into the CCR4-NOT complex.
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DOI：
10.1016/j.jmb.2022.167523
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发表时间：
2022-03
影响因子：
5.6
通讯作者：
P. Stoney;Akiko Yanagiya;Saori Nishijima;Tadashi Yamamoto
中科院分区：
文献类型：
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作者：
P. Stoney;Akiko Yanagiya;Saori Nishijima;Tadashi Yamamoto
CCR4-Not Deadenylase复合体是真核基因表达的主要转录后调控因子。Cnot7和CNOT8都是酵母CCR4-非催化亚基CAF1的脊椎动物同源物。它们高度相似，有时被认为是多余的，但Cnot7和Cnot8基因敲除小鼠表现出不同的表型，意味着不同的生理功能。在本研究中，我们揭示了Cnot7对CNOT8的非互惠作用，在Cnot7缺失的情况下，CNOT8蛋白增加，而CNOT8的mRNA水平没有相应的变化，而Cnot7不受CNOT8丢失的影响。Cnot8mRNA可能与CCR4-非复合体结合，提示CCR4-不直接调节CNOT8的表达。Cnot8mRNA相对不稳定，但Cnot7基因敲除不稳定Cnot8mRNA，也不增加翻译。CNOT8蛋白的稳定性也不如Cnot7。Cnot7比CNOT8对CCR4-NOT支架蛋白CNOT1具有更强的亲和力，并能阻断CNOT8与CNOT1的结合。Cnot7的缺失增加了CNOT8对CCR4-NOT复合体的掺入，并稳定了CNOT8。这些数据表明，Cnot7是CCR4-NOT中的主要平行序列，Cnot7和CNOT8蛋白的稳定性以不同的方式受到调节。
The CCR4-NOT deadenylase complex is a major post-transcriptional regulator of eukaryotic gene expression. CNOT7 and CNOT8 are both vertebrate homologs of the yeast CCR4-NOT catalytic subunit Caf1. They are highly similar and are sometimes considered redundant, butCnot7andCnot8knockout mice exhibit different phenotypes, implying distinct physiological functions. In this study, we reveal a non-reciprocal effect of CNOT7 on CNOT8, in which CNOT8 protein is increased in the depletion of CNOT7 without corresponding changes in mRNA levels whereas CNOT7 is not affected by the loss of CNOT8.Cnot8mRNA may be bound by the CCR4-NOT complex, suggesting that CCR4-NOT might directly regulate CNOT8 expression.Cnot8mRNA is relatively unstable, butCnot7knockdown did not stabilizeCnot8mRNA, nor did it increase translation. CNOT8 protein was also less stable than CNOT7. CNOT7 showed greater affinity than CNOT8 for the CCR4-NOT scaffold protein CNOT1 and was able to block CNOT8 from binding to CNOT1. Depletion of CNOT7 increased CNOT8 incorporation into the CCR4-NOT complex and stabilized CNOT8. These data suggest that CNOT7 is the dominant paralog in CCR4-NOT and that CNOT7 and CNOT8 protein stability is regulated in distinct ways.