IntS6 and the Integrator phosphatase module tune the efficiency of select premature transcription termination events.
IntS6 and the Integrator phosphatase module tune the efficiency of select premature transcription termination events.
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IntS6 和 Integrator 磷酸酶模块可调节选定的过早转录终止事件的效率。
DOI：
10.1016/j.molcel.2023.10.035
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发表时间：
2023
期刊：
影响因子：
16
通讯作者：
Wilusz,JeremyE
中科院分区：
文献类型：
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作者：
Fujiwara,Rina;Zhai,Si-Nan;Liang,Dongming;Shah,AayushiP;Tracey,Matthew;Ma,Xu-Kai;Fields,ChristopherJ;Mendoza-Figueroa,MaríaSaraí;Meline,MicheleC;Tatomer,DeirdreC;Yang,Li;Wilusz,JeremyE
后生动物特异性整合子复合物催化小核RNA（snRNA）的3′端加工和提前终止，从而减弱许多蛋白质编码基因的转录。整合子具有RNA内切酶和蛋白磷酸酶活性，但尚不清楚这两者是否是复杂功能所必需的。在这里，我们显示IntS6（整合子亚基6）过表达阻断了果蝇蛋白质编码基因亚群中整合子的功能，尽管对snRNA或其他位点的衰减没有影响。过表达IntS6蛋白磷酸酶2A（PP2A）亚基，从而仅影响磷酸酶活性对整合子功能是必需的基因位点。IntS6的功能类似于PP2A调节B亚基，因为不结合整合子的典型B亚基的过表达也足以抑制整合子活性。这些结果表明，磷酸酶模块是关键的，只有一个子集的整合调控的基因，并指出PP2A招聘作为一个可调的步骤，调节转录终止效率。
The metazoan-specific Integrator complex catalyzes 3′ end processing of small nuclear RNAs (snRNAs) and premature termination that attenuates the transcription of many protein-coding genes. Integrator has RNA endonuclease and protein phosphatase activities, but it remains unclear if both are required for complex function. Here, we show IntS6 (Integrator subunit 6) over-expression blocks Integrator function at a subset ofDrosophilaprotein-coding genes, although having no effect on snRNAs or attenuation of other loci. Over-expressed IntS6 titrates protein phosphatase 2A (PP2A) subunits, thereby only affecting gene loci where phosphatase activity is necessary for Integrator function. IntS6 functions analogous to a PP2A regulatory B subunit as over-expression of canonical B subunits, which do not bind Integrator, is also sufficient to inhibit Integrator activity. These results show that the phosphatase module is critical at only a subset of Integrator-regulated genes and point to PP2A recruitment as a tunable step that modulates transcription termination efficiency.