Matrin 3 Binds and Stabilizes mRNA

Abstract

Matrin 3 (MATR3) is a highly conserved, inner nuclear matrix protein with two zinc finger domains and two RNA recognition motifs (RRM), whose function is largely unknown. Recently we found MATR3 to be phosphorylated by the protein kinase ATM, which activates the cellular response to double strand breaks in the DNA. Here, we show that MATR3 interacts in an RNA-dependent manner with several proteins with established roles in RNA processing, and maintains its interaction with RNA via its RRM2 domain. Deep sequencing of the bound RNA (RIP-seq) identified several small noncoding RNA species. Using microarray analysis to explore MATR3′s role in transcription, we identified 77 transcripts whose amounts depended on the presence of MATR3. We validated this finding with nine transcripts which were also bound to the MATR3 complex. Finally, we demonstrated the importance of MATR3 for maintaining the stability of several of these mRNA species and conclude that it has a role in mRNA stabilization. The data suggest that the cellular level of MATR3, known to be highly regulated, modulates the stability of a group of gene transcripts.

RNA-binding proteins in neurodegeneration: mechanisms in aggregate

“…1; Johnson et al 2014). Matrin-3 is a DNA-and RNA-binding protein with a role in promoting mRNA stability (Salton et al 2011) and has also been suggested to associate with TDP-43 (Ling et al 2010), although the interaction was shown to be RNA-dependent (Johnson et al 2014). While the precise nature of Matrin-3 in cellular granules with other disease-related proteins in unclear, such findings reinforce the convergence of different ALS genes in the same physical processes.…”

Proteomic Analysis of Epithelial to Mesenchymal Transition (EMT) Reveals Cross-talk between SNAIL and HDAC1 Proteins in Breast Cancer Cells

“…Of note, some of these proteins are very abundant in normal breast tissue, such as MATR3 (Matrin-3), CPSF7 (Cleavage and Polyadenylation Specificity Factor Subunit 7), DX39B (Spliceosome RNA Helicase DDX39B), and HDAC1 (Histone Deacetylase 1), and all were down-regulated during EMT and also in the aggressive phenotype of MDA-MB-231. MATR3 plays a role in transcription, may interact with other nuclear matrix proteins, and binds to mRNA (43). CPFS7 is a component of the cleavage factor Im complex that plays a key role in pre-mRNA 3Ј-processing, binds to cleavage and polyadenylation RNA substrates, and is a target of miR-26b, which is a potent regulator of cancer behavior in estrogen receptor-positive cancers (44).…”

Proteomics of tissue factor silencing in cardiomyocytic cells reveals a new role for this coagulation factor in splicing machinery control

“…One new finding is that TF silencing profoundly down-regulated the expression of matrin 3, a 407 highly conserved inner nuclear matrix protein which, through a direct interaction with hnRNP 408 proteins and with the DNA and RNA helicase DHX9, might control RNA metabolism and 409 stabilisation [50]. 410…”