Howard Hughes Medical Institute.
Genes Dev. 2012 Dec 15;26(24):2690-5. doi: 10.1101/gad.204602.112.
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.
RNA 结合蛋白 FUS（肉瘤中融合）/TLS 的突变已被证明会导致神经退行性疾病肌萎缩侧索硬化症（ALS），但 FUS 的正常作用尚不完全清楚。我们发现 FUS 结合 RNA 聚合酶 II（RNAP2）的 C 端结构域（CTD），并防止数千个人类基因中 RNAP2 CTD 的 Ser2 发生不当过度磷酸化。FUS 的缺失导致 RNAP2 在转录起始位点的积累，并导致 mRNA 异构体表达向早期多聚腺苷酸化位点转移。因此，除了在选择性 RNA 剪接中的作用外，FUS 在 RNAP2 转录过程中协调 CTD 磷酸化方面具有普遍功能。
