N-terminal sequences in matrin 3 mediate phase separation into droplet-like structures that recruit TDP43 variants lacking RNA binding elements.

RNA binding proteins associated with amyotrophic lateral sclerosis (ALS) and muscle myopathy possess sequence elements that are low in complexity, or bear resemblance to yeast prion domains. These sequence elements appear to mediate phase separation into liquid-like membraneless organelles. Using fusion proteins of matrin 3 (MATR3) to yellow fluorescent protein (YFP), we recently observed that deletion of the second RNA recognition motif (RRM2) caused the protein to phase separate and form intranuclear liquid-like droplets.

Characterization of gene regulation and protein interaction networks for Matrin 3 encoding mutations linked to amyotrophic lateral sclerosis and myopathy.

To understand how mutations in Matrin 3 (MATR3) cause amyotrophic lateral sclerosis (ALS) and distal myopathy, we used transcriptome and interactome analysis, coupled with microscopy. Over-expression of wild-type (WT) or F115C mutant MATR3 had little impact on gene expression in neuroglia cells. Only 23 genes, expressed at levels of >100 transcripts showed ≥1.