Matrin3 regulates mitotic spindle dynamics by controlling alternative splicing of CDC14B

Author:

Muys, Bruna R

Shrestha, Roshan L

Anastasakis, Dimitrios G

Pongor, Lorinc

Li, Xiao Ling

Grammatikakis, Ioannis

Polash, Ahsan

Chari,Raj

Gorospe, Myriam

Harris, Curtis C

Aladjem, Mirit I

Basrai, Munira A

Hafner, Markus

Lal, Ashish
Author Address

Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), Bethesda, MD 20892, USA., Genetics Branch, CCR, NCI, Bethesda, MD 20892, USA., RNA Molecular Biology Laboratory, National Institute for Arthritis and Musculoskeletal and Skin Disease, Bethesda, MD 20892, USA., Developmental Therapeutics Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA., Genome Modification Core, Frederick National Lab for Cancer Research, Frederick, MD 21701, USA., Laboratory of Genetics and Genomics, National Institute on Aging, Baltimore, MD 21224, USA., Laboratory of Human Carcinogenesis, CCR, NCI, Bethesda, MD 20892, USA., RNA Molecular Biology Laboratory, National Institute for Arthritis and Musculoskeletal and Skin Disease, Bethesda, MD 20892, USA. Electronic address: markus.hafner@nih.gov., Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), Bethesda, MD 20892, USA. Electronic address: ashish.lal@nih.gov.,

Abstract:

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.

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