Alternative polyadenylation factor CPSF6 regulates temperature compensation of the mammalian circadian clock.
Alternative polyadenylation factor CPSF6 regulates temperature compensation of the mammalian circadian clock.
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替代聚腺苷酸化因子CPSF6调节哺乳动物昼夜节律时钟的温度补偿。
DOI：
10.1371/journal.pbio.3002164
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发表时间：
2023-06
期刊：
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
--
作者：
生物钟的一个决定性特性是温度补偿，其特征是其近 24 小时自由运行期对生理范围内环境温度变化的恢复能力。虽然温度补偿在不同的生命类群中是进化保守的，并且已经在许多模式生物中进行了研究，但其分子基础仍然难以捉摸。转录后调控，例如温度敏感的选择性剪接或磷酸化，已被描述为潜在反应。在这里，我们发现，裂解和聚腺苷酸化特异性因子亚基 6 (CPSF6)（3'端裂解和聚腺苷酸化的关键调节因子）的敲低可显着改变人类 U-2 OS 细胞的昼夜温度补偿。我们结合使用 3'-end-RNA-seq 和基于质谱的蛋白质组学来全面量化 3'UTR 长度的变化以及野生型和 CPSF6 敲低细胞之间的基因和蛋白质表达及其对温度的依赖性。由于温度补偿行为的变化应反映在 3 个调节层之一或全部内温度响应的变化中，因此我们统计评估了野生型和 CPSF6 敲低细胞之间环境温度变化时的差异响应。通过这种方式，我们揭示了昼夜温度补偿的候选基因，包括真核翻译起始因子 2 亚基 1 (EIF2S1)。这项研究表明，替代多聚腺苷酸化因子 CPSF6 的敲除会影响人体细胞中昼夜节律自由运行期对环境温度变化的恢复能力；多组学方法揭示了这种温度补偿背后的候选基因。
A defining property of circadian clocks is temperature compensation, characterized by the resilience of their near 24-hour free-running periods against changes in environmental temperature within the physiological range. While temperature compensation is evolutionary conserved across different taxa of life and has been studied within many model organisms, its molecular underpinnings remain elusive. Posttranscriptional regulations such as temperature-sensitive alternative splicing or phosphorylation have been described as underlying reactions. Here, we show that knockdown of cleavage and polyadenylation specificity factor subunit 6 (CPSF6), a key regulator of 3′-end cleavage and polyadenylation, significantly alters circadian temperature compensation in human U-2 OS cells. We apply a combination of 3′-end-RNA-seq and mass spectrometry–based proteomics to globally quantify changes in 3′ UTR length as well as gene and protein expression between wild-type and CPSF6 knockdown cells and their dependency on temperature. Since changes in temperature compensation behavior should be reflected in alterations of temperature responses within one or all of the 3 regulatory layers, we statistically assess differential responses upon changes in ambient temperature between wild-type and CPSF6 knockdown cells. By this means, we reveal candidate genes underlying circadian temperature compensation, including eukaryotic translation initiation factor 2 subunit 1 (EIF2S1). This study shows that knockdown of the alternative polyadenylation factor CPSF6 affects the resilience of the circadian free-running period against changes in environmental temperature in human cells; a multi-omics approach reveals candidate genes underlying such temperature compensation.
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影响因子：
7
作者：
Derr A;Yang C;Zilionis R;Sergushichev A;Blodgett DM;Redick S;Bortell R;Luban J;Harlan DM;Kadener S;Greiner DL;Klein A;Artyomov MN;Garber M
通讯作者：
Garber M
影响因子：
10.5
作者：
Diernfellner, ACR;Schafmeier, T;Brunner, M
通讯作者：
Brunner, M
影响因子：
64.8
作者：
Endo, Motomu;Shimizu, Hanako;Nohales, Maria A.;Araki, Takashi;Kay, Steve A.
通讯作者：
Kay, Steve A.
DOI：
10.1073/pnas.0707772105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Brown, Steven A.;Kunz, Dieter;Kramer, Achim
通讯作者：
Kramer, Achim
影响因子：
4.4
作者：
Eyring, H
通讯作者：
Eyring, H