Casein kinase II promotes target silencing by miRISC through direct phosphorylation of the DEAD-box RNA helicase CGH-1
Casein kinase II promotes target silencing by miRISC through direct phosphorylation of the DEAD-box RNA helicase CGH-1
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DOI：
10.1073/pnas.1509499112
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发表时间：
2015-12-29
影响因子：
11.1
通讯作者：
Kim, John K.
中科院分区：
文献类型：
--
作者：
Alessi, Amelia F.;Khivansara, Vishal;Kim, John K.
microRNAs（miRNAs）通过与miRNAs诱导的沉默复合体（miRISC）结合，在多种发育过程中发挥重要的保守作用。尽管已经建立了对miRNA生物发生和靶基因沉默的机制框架的基本见解，但影响miRISC功能的翻译后修饰还不太清楚。在这里，我们报告，保守的丝氨酸/苏氨酸激酶，酪蛋白激酶II（CK 2），促进秀丽隐杆线虫miRISC功能。CK 2失活导致发育缺陷，即miRISC辅因子的表型丢失，并在不同的细胞环境中增强miRNA功能的丧失。尽管CK 2对于miRNA生物发生和miRISC辅因子的稳定性是必需的，但它对于有效的miRISC靶mRNA结合和沉默是必需的。重要的是，我们确定了保守的DEAD盒RNA解旋酶CGH-1/DDX 6作为miRISC中的关键CK 2底物，并证明了保守的N-末端丝氨酸的磷酸化是miRNA途径中CGH-1功能所必需的。
MicroRNAs (miRNAs) play essential, conserved roles in diverse developmental processes through association with the miRNA-induced silencing complex (miRISC). Whereas fundamental insights into the mechanistic framework of miRNA biogenesis and target gene silencing have been established, posttranslational modifications that affect miRISC function are less well understood. Here we report that the conserved serine/threonine kinase, casein kinase II (CK2), promotes miRISC function in Caenorhabditis elegans. CK2 inactivation results in developmental defects that phenocopy loss of miRISC cofactors and enhances the loss of miRNA function in diverse cellular contexts. Whereas CK2 is dispensable for miRNA biogenesis and the stability of miRISC cofactors, it is required for efficient miRISC target mRNA binding and silencing. Importantly, we identify the conserved DEAD-box RNA helicase, CGH-1/DDX6, as a key CK2 substrate within miRISC and demonstrate phosphorylation of a conserved N-terminal serine is required for CGH-1 function in the miRNA pathway.