The role of MATRIN3 (MATR3) in innate immune response

Abstract MATR3, one of the most abundant inner nuclear matrix proteins, is implicated in amyotrophic lateral sclerosis (ALS) and distal myopathy. MATR3 has been reported to have both DNA- RNA-binding abilities. However, it not understood mechanistically how mutation leads ALS pathogenesis. To understand its loss function effects, we mutated human HAP1 cell line using CRISPR/Cas9 technology. Using two different RNA sequencing methods, Oxford Nanopore Technologies Illumina, discovered upregulation many interferon-stimulated genes (ISGs) MATR3-deficient cells. Furthermore, validated these results by Nanostring Next, hypothesized that cells may be responding endogenous double-stranded RNAs. Interestingly, observed similar amounts dsRNA knock-out (KO) wildtype (WT) which suggests indeed intracellular dsRNAs are present could stimulating cells; however, case KO stimulated because they producing significantly more dsRNAs. Currently, investigating whether sensors activated Also, MATR3’s and/or abilities responsible for innate immune response. Accordingly, plan perform CUT & RUN photoactivatable ribonucleoside enhanced crosslinking immunoprecipitation (PAR-CLIP) respectively, Altogether, our illustrate a novel negative regulator This work was supported Intramural Research Program NIAID, NIH.