Matrin3 regulates mitotic spindle dynamics by controlling alternative splicing of CDC14B
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
Affiliations
Bruna R. Muys
Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), Bethesda, MD 20892, USA
Roshan L. Shrestha
Genetics Branch, CCR, NCI, Bethesda, MD 20892, USA
Dimitrios G. Anastasakis
RNA Molecular Biology Laboratory, National Institute for Arthritis and Musculoskeletal and Skin Disease, Bethesda, MD 20892, USA
Lorinc Pongor
Developmental Therapeutics Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA
Xiao Ling Li
Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), Bethesda, MD 20892, USA
Ioannis Grammatikakis
Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), Bethesda, MD 20892, USA
Ahsan Polash
RNA Molecular Biology Laboratory, National Institute for Arthritis and Musculoskeletal and Skin Disease, Bethesda, MD 20892, USA
Raj Chari
Genome Modification Core, Frederick National Lab for Cancer Research, Frederick, MD 21701, USA
Myriam Gorospe
Laboratory of Genetics and Genomics, National Institute on Aging, Baltimore, MD 21224, USA
Curtis C. Harris
Laboratory of Human Carcinogenesis, CCR, NCI, Bethesda, MD 20892, USA
Mirit I. Aladjem
Developmental Therapeutics Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA
Munira A. Basrai
Genetics Branch, CCR, NCI, Bethesda, MD 20892, USA
Markus Hafner
RNA Molecular Biology Laboratory, National Institute for Arthritis and Musculoskeletal and Skin Disease, Bethesda, MD 20892, USA; Corresponding author
Ashish Lal
Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), Bethesda, MD 20892, USA; Corresponding author
Summary: 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.
