Molecular determinants and modifiers of Matrin-3 toxicity, condensate dynamics, and droplet morphology

Sprunger, Macy L.; Lee, Ken; Sohn, Brian S.; Jackrel, Meredith E.

doi:10.1016/j.isci.2022.103900

Cited by 18 publications

(22 citation statements)

References 93 publications

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“…This protocol describes the steps to analyze condensates of MATR3-eGFP in live S. cerevisiae cells by FRAP ( Sprunger et al., 2022 ). We have also used this protocol for analysis of FUS-CHOP-GFP in yeast ( Ryan et al., 2019 ).…”

Section: Before You Beginmentioning

confidence: 99%

“…This protocol can be broadly applied to study condensate dynamics of a range of proteins in different model systems. For complete details on the use and execution of this protocol, please refer to Sprunger et al. (2022) .…”

mentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Sprunger et al. (2022) .…”

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confidence: 99%

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Monitoring condensate dynamics in S. cerevisiae using fluorescence recovery after photobleaching

Sprunger

Jackrel²

2022

STAR Protocols

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Section: Before You Beginmentioning

confidence: 99%

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confidence: 99%

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Monitoring condensate dynamics in S. cerevisiae using fluorescence recovery after photobleaching

Sprunger

Jackrel²

2022

STAR Protocols

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“…Even though Matrin3 appears to be essential in vivo , disease-associated mutations were primarily found in neurodegenerative disorders, e.g., in familial Amyotrophic Lateral Sclerosis (ALS) and frontotemporal dementia (FTD) 21 . The impaired formation of dynamic nuclear condensates due to ALS-associated mutations in Matrin3 possibly contributes to its pathogenic mechanism 22 . There is conflicting evidence for a role of Matrin3 in cancer with some studies indicating a potential role of Matrin3 as an oncogene and other studies suggesting a tumor suppressive function 23–25 .…”

Section: Introductionmentioning

confidence: 99%

Matrin3 regulates cell proliferation and spindle dynamics by regulating CDC14B alternative splicing

Muys

Shrestha

Anastasakis

et al. 2022

Preprint

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Matrin3 is an RNA-binding protein that affects diverse RNA-related processes, including mRNA splicing. While Matrin3 has been intensively studied in neurodegenerative diseases, its function in cancer remains unclear. Here, we discovered Matrin3-mediated regulation of mitotic spindle dynamics in colorectal cancer (CRC) cells. We identified bound and regulated Matrin3-target RNAs transcriptome-wide in CRC cells and found that Matrin3 broadly modulates mRNA splicing patterns. Among the top Matrin3 targets, we focused on CDC14B and found that Matrin3 loss increased inclusion of an exon containing a premature termination codon into the CDC14B transcript and simultaneous down-regulation of the standard CDC14B transcript. Selective knockdown of the CDC14B standard transcript phenocopied Matrin3 knockdown and exhibited reduced proliferation and defects in mitotic spindle formation, suggesting that CDC14B is a key downstream effector of Matrin3. Collectively, these data reveal an important role for the Matrin3/CDC14B axis in control of CRC cell proliferation and mitotic spindle formation.

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“…[5][6] MATR3 is a DNA and RNA binding protein, and genetic changes in the MATR3 gene play a role in the biology of neurodegenerative disorders. [7][8] In cancer, MATR3 was recognized as one of the ve genes deleted from chromosome 5 of primary, metastasized and xenografted human basal-like breast cancer (BLBC), which allowed to propose a tumor suppressive function of this gene. [9] However, to date the biological role and prognostic relevance of MATR3 in human cancers remain largely underexplored.…”

Section: Introductionmentioning

confidence: 99%

Low expression of MATR3 is associated with poor survival in clear cell renal cell carcinoma

Durślewicz

Klimaszewska‐Wiśniewska

Antosik

et al. 2022

Preprint

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Matrin 3 (MATR3) is one of the most abundant inner nuclear matrix proteins involved in multiple nuclear processes. To date the biological role and prognostic relevance of MATR3 in human cancers remain largely underexplored. Therefore, the aim of the present study was to examine the expression levels and prognostic significance of MATR3 in clear cell renal cell carcinoma (ccRCC) patients. We assessed MATR3 immunohistochemical staining and RNA-seq data from publicly available data sets, and the results were analyzed with reference to clinicopathological characteristics and overall survival of patients. Furthermore, protein-protein interaction (PPI) network for MATR3 and its neighbors was constructed, functionally annotated, and screened for survival-related genes. We observed that MATR3 protein and mRNA levels were lower in tumor tissues compared to control tissues. Lower MATR3 protein and mRNA expression levels were found to be a significant independent adverse prognostic factor for patient overall survival (OS). Moreover, out of the candidate genes, MRPL23 gene was identified as being the most predictive of OS and combined MRPL23/MATR3 expression status predicted patient survival better than looking at each marker individually. In conclusion, the present investigation warrants further research into the biological and prognostic value of MATR3 and MRPL23 in ccRCC patients.

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Molecular determinants and modifiers of Matrin-3 toxicity, condensate dynamics, and droplet morphology

Cited by 18 publications

References 93 publications

Monitoring condensate dynamics in S. cerevisiae using fluorescence recovery after photobleaching

Monitoring condensate dynamics in S. cerevisiae using fluorescence recovery after photobleaching

Matrin3 regulates cell proliferation and spindle dynamics by regulating CDC14B alternative splicing

Low expression of MATR3 is associated with poor survival in clear cell renal cell carcinoma

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