Mutations in the MATR3 gene encoding the nucleotide binding protein Matrin 3 have recently been identified as causing a subset of familial amyotrophic lateral sclerosis (fALS) and more rarely causing distal myopathy. Translating the identification of MATR3 mutations into an understanding of disease pathogenesis and the creation of mouse models requires a complete understanding of normal Matrin 3 levels and distribution in vivo. Consequently, we examined the levels of murine Matrin 3 in body tissues and regions of the central nervous system (CNS). We observed a significant degree of variability in Matrin 3 protein levels among different tissues of adult animals, with the highest levels found in reproductive organs and the lowest in muscle. Within the adult CNS, Matrin 3 levels were lowest in spinal cord. Further, we found that Matrin 3 declines significantly in CNS through early development and young adulthood before stabilizing. As previously reported, antibodies to Matrin 3 primarily stain nuclei, but the intensity of staining was not uniform in all nuclei. The low levels of Matrin 3 in spinal cord and muscle could mean that that these tissues are particularly vulnerable to alterations in Matrin 3 function. Our study is the first to characterize endogenous Matrin 3 in rodents across the lifespan, providing the groundwork for deciphering disease mechanisms and developing mouse models of MATR3-linked ALS. J. Comp. Neurol. 524:2740-2752, 2016. © 2016 Wiley Periodicals, Inc.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832027 | PMC |
| http://dx.doi.org/10.1002/cne.23986 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The nuclear matrix stabilizes primed-specific genes in human pluripotent stem cells.
Nat Cell Biol
January 2025
Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.
The nuclear matrix, a proteinaceous gel composed of proteins and RNA, is an important nuclear structure that supports chromatin architecture, but its role in human pluripotent stem cells (hPSCs) has not been described. Here we show that by disrupting heterogeneous nuclear ribonucleoprotein U (HNRNPU) or the nuclear matrix protein, Matrin-3, primed hPSCs adopted features of the naive pluripotent state, including morphology and upregulation of naive-specific marker genes. We demonstrate that HNRNPU depletion leads to increased chromatin accessibility, reduced DNA contacts and increased nuclear size.
View Article and Find Full Text PDFLiver matrin-3 protects mice against hepatic steatosis and stress response via constitutive androstane receptor.
Mol Metab
August 2024
Department of Biochemistry, University of Nebraska - Lincoln, Beadle Center, 1901 Vine St, Lincoln, NE 68588, USA; Nebraska Center for Integrated Biomolecular Communication (NCIBC), University of Nebraska - Lincoln, Lincoln, NE 68588, USA; Nebraska Center for the Prevention of Obesity Diseases through Dietary Molecules, University of Nebraska - Lincoln, USA. Electronic address:
Article Synopsis
- Researchers are studying a liver disease called MASLD, which is getting more common because many people are becoming overweight, and they want to find better treatments.
- They looked at a protein called Matrin-3 that helps control how genes work in the liver and its role in preventing fat buildup and stress responses.
- When Matrin-3 was removed from certain mice, it made their livers worse when they ate a high-fat diet, showing that Matrin-3 is important for keeping liver health by helping a special receptor called CAR function properly.
MATR3's Role beyond the Nuclear Matrix: From Gene Regulation to Its Implications in Amyotrophic Lateral Sclerosis and Other Diseases.
Cells
June 2024
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada.
Matrin-3 (MATR3) was initially discovered as a component of the nuclear matrix about thirty years ago. Since then, accumulating studies have provided evidence that MATR3 not only plays a structural role in the nucleus, but that it is also an active protein involved in regulating gene expression at multiple levels, including chromatin organization, DNA transcription, RNA metabolism, and protein translation in the nucleus and cytoplasm. Furthermore, MATR3 may play a critical role in various cellular processes, including DNA damage response, cell proliferation, differentiation, and survival.
View Article and Find Full Text PDFThe role of Matrin-3 in physiology and its dysregulation in disease.
Biochem Soc Trans
June 2024
Department of Chemistry, Washington University, St. Louis, MO 63130, U.S.A.
The dysfunction of many RNA-binding proteins (RBPs) that are heavily disordered, including TDP-43 and FUS, are implicated in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). These proteins serve many important roles in the cell, and their capacity to form biomolecular condensates (BMCs) is key to their function, but also a vulnerability that can lead to misregulation and disease. Matrin-3 (MATR3) is an intrinsically disordered RBP implicated both genetically and pathologically in ALS/FTD, though it is relatively understudied as compared with TDP-43 and FUS.
View Article and Find Full Text PDFMATR3 pathogenic variants differentially impair its cryptic splicing repression function.
FEBS Lett
February 2024
Department of Molecular Genetics, University of Toronto, Canada.
Article Synopsis
- MATR3 is an RNA-binding protein connected to neurodegenerative and neurodevelopmental diseases, but its role in cryptic splicing is not well understood.
- Loss of MATR3 leads to the inclusion of cryptic exons in various transcripts, significantly affecting gene function.
- Disease-associated variants, like S85C and M548T, impact MATR3 by reducing its solubility and altering its ability to bind RNA and regulate cryptic splicing.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!