Damage to RNA processing Sample Clauses

Damage to RNA processing. The first evidence that aberrant mRNA processing could be a disease mechanism in ALS came from studies of ALS tissue samples (Xxx et al., 1998). Specifically, faulty splicing of the mRNA coding for the glial glutamate transporter, excitatory amino acid transporter 2 (EAAT2), was found in ALS patients (Xxx et al., 1998). More recently, genetic studies have provided more evidence for aberrant RNA metabolism in ALS. Mutations in TDP-43, FUS, SETX, ANG and ATXN2 have been found in some cases of FALS and all of these proteins have functions in mRNA processing (Xxxx et al., 2004; Xxxxxxxxxx et al., 2008; Xxxxxxxxxxx et al., 2009; Xxxxx et al., 2009; Xxxxx et al., 2010; Xxxxx and Xxxxxx, 2013). In addition, the intronic GGGGCC hexanucleotide expansion in C9ORF72 which is the most common genetic cause of SALS, FALS and FTD has been linked to abnormal RNA metabolism (XxXxxxx-Xxxxxxxxx et al., 2011; Xxxxxx et al., 2011; Xxxxxx-Knock et al., 2012). C9ORF72 encodes an uncharacterised protein and expression of mutant C9ORF72 leads to the formation of nuclear RNA foci (XxXxxxx-Xxxxxxxxx et al., 2011). Research indicates that mRNA binding proteins are sequestered in these foci which might lead to a disruption in mRNA metabolism (XxXxxxx-Xxxxxxxxx et al., 2011). Thus, mutant C9ORF72 mRNA itself may be toxic.