FUS binds the CTD of RNA polymerase II and regulates its phosphorylation at Ser2

被引:177
作者
Schwartz, Jacob C. [1 ,2 ,3 ]
Ebmeier, Christopher C. [2 ]
Podell, Elaine R. [1 ,2 ,3 ]
Heimiller, Joseph [4 ]
Taatjes, Dylan J. [2 ]
Cech, Thomas R. [1 ,2 ,3 ]
机构
[1] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA
[2] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA
[3] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA
[4] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA
关键词
FUS; P-TEFb; RNA-binding protein; TLS; transcription; AMYOTROPHIC-LATERAL-SCLEROSIS; C-TERMINAL DOMAIN; TRANSCRIPTION; GENE; ELONGATION; TRANSITION; MUTATIONS; FUS/TLS; COMPLEX; PROTEIN;
D O I
10.1101/gad.204602.112
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mutations in the RNA-binding protein FUS (fused in sarcoma)/TLS have been shown to cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS), but the normal role of FUS is incompletely understood. We found that FUS binds the C-terminal domain (CTD) of RNA polymerase II (RNAP2) and prevents inappropriate hyperphosphorylation of Ser2 in the RNAP2 CTD at thousands of human genes. The loss of FUS leads to RNAP2 accumulation at the transcription start site and a shift in mRNA isoform expression toward early polyadenylation sites. Thus, in addition to its role in alternative RNA splicing, FUS has a general function in orchestrating CTD phosphorylation during RNAP2 transcription.
引用
收藏
页码:2690 / 2695
页数:6
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