Expression of CELF proteins Sample Clauses

Expression of CELF proteins. The expression of CELF proteins is developmentally regulated in the heart and striated muscle (Xxxx et al., 2001). All CELF proteins are expressed in adult and foetal brain (Xxxx et al., 2004). In all tissues examined, there is expression of at least one or more CELF protein with the exception of CELF3 and CELF5 whose expression are restricted to the brain while CELF2 and CELF4 are developmentally regulated in striated muscle and heart (Xxxx et al., 2001); (Xxxx et al., 2004); (Xxxx et al., 2005) (Table 1.3). CELF proteins are localised in the nucleus and cytoplasm, conforming to their role as multifunctional proteins. CELF1 has multiple roles including regulation of alternative splicing in the nucleus; as well as mRNA translation (through its activity at the 5’ end) and mRNA degradation (at the 3’ end in the cytoplasm) (Xxxxxxxxx et al., 1996) (Xxxxxxx et al., 2006; Xxxxxxxx et al., 2003). CELF proteins are localised to the nucleus by their NLS sequences at the C-terminal, within RRM3 (Xxxxxxx et al., 2007; Xxxx et al., 2001). This NLS motif located within RRM3 is conserved in all members of the CELF family; with the basic amino acid sequence KRXK. CELF proteins bind specifically to CUG repeats in intronic elements or in the 3’- UTR (untranslated region) of pre-mRNA and mRNA transcripts (Xxxxxxxx and Xxxxxx, 2005; Xxxx et al., 2001). Several CELF proteins have been implicated in the regulation of tau alternative splicing including CELF2, CELF3 and CELF4 (Xxxxxxx et al., 2007; Xxxxx et al., 2006; Xxxx et al., 2004). During alternative splicing of the MAPT gene, CELF proteins bind to intronic elements around alternative exons including exon 2 and 10 to govern their inclusion or exclusion in the mature tau mRNA (Xxxxxxxxx, 2005). It is therefore paramount that the expression levels of these splicing factors in response to cellular stimuli is accurate to ensure precise alternative splicing of tau transcripts as well as their other pre-mRNA targets during splicing.
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