Matrin3 通过控制CDC14B的替代剪接调控有丝分裂纺锤动力学。
Matrin3 regulates mitotic spindle dynamics by controlling alternative splicing of CDC14B.
发表日期:2023 Mar 15
作者:
Bruna R Muys, Roshan L Shrestha, Dimitrios G Anastasakis, Lorinc Pongor, Xiao Ling Li, Ioannis Grammatikakis, Ahsan Polash, Raj Chari, Myriam Gorospe, Curtis C Harris, Mirit I Aladjem, Munira A Basrai, Markus Hafner, Ashish Lal
来源:
Cellular & Molecular Immunology
摘要:
Matrin3是一种RNA结合蛋白,在多种RNA相关进程中调节,包括mRNA剪接。尽管Matrin3在神经退行性疾病方面已经得到深入研究,但在癌症中的功能仍不清楚。在这里,我们报告了Matrin3在结直肠癌(CRC)细胞中介导调节有丝分裂纺锤体动态的作用。我们全面确定了CRC细胞中Matrin3所结合和调节的RNA,并关注其中一个重要的Matrin3靶标CDC14B。Matrin3敲除导致CDC14B转录物中包含一个早期终止密码子的外显子的包含率增加,同时标准的CDC14B转录物下调。CDC14B的敲除导致有丝分裂纺锤体动态的缺陷,与Matrin3敲除效果相似。在Matrin3过度表达时,纺锤体的延长和错向现象得到了解救,这表明CDC14B是Matrin3的一个关键下游效应因子。总之,这些数据揭示了Matrin3 / CDC14B轴在控制有丝分裂纺锤体动态方面的作用。
Matrin3 is an RNA-binding protein that regulates diverse RNA-related processes, including mRNA splicing. Although Matrin3 has been intensively studied in neurodegenerative diseases, its function in cancer remains unclear. Here, we report Matrin3-mediated regulation of mitotic spindle dynamics in colorectal cancer (CRC) cells. We comprehensively identified RNAs bound and regulated by Matrin3 in CRC cells and focused on CDC14B, one of the top Matrin3 targets. Matrin3 knockdown results in increased inclusion of an exon containing a premature termination codon in the CDC14B transcript and simultaneous down-regulation of the standard CDC14B transcript. Knockdown of CDC14B phenocopies the defects in mitotic spindle dynamics upon Matrin3 knockdown, and the elongated and misoriented mitotic spindle observed upon Matrin3 knockdown are rescued upon overexpression of CDC14B, suggesting that CDC14B is a key downstream effector of Matrin3. Collectively, these data reveal a role for the Matrin3/CDC14B axis in control of mitotic spindle dynamics.Published by Elsevier Inc.