In addition to MBNL proteins, the splicing regulators hnRNP H and F colo-calize with CUG foci in neurons of DM1 patient brain samples (Jiang et al. 2004). Neuron-specific c-src N1 exon is regulated by hnRNP F (Min et al. 1995) and hnRNP H regulates NF-1 exon 3, thyroid stimulating hormone beta subunit (TSH beta) genes (Buratti et al. 2004), HIV-1 tev-specific exon 6D (Caputi and Zahler 2002) and beta tropomyosin (Chen et al. 1999). The relevance of hnRNP H and hnRNP F colocalization with RNA foci is not clear since splicing of c-src is not disrupted in neurons (Jiang et al. 2004).
Double-stranded-RNA-dependent protein kinase R (PKR), is activated by double-stranded RNA as a response to viral infections (Williams 2001). Activation of PKR inhibits translation by phosphorylation of translation initiation factor eIF2 alpha (Clemens 2001). PKR was identified as one of the RNA-binding proteins that bind to double-stranded CUG repeats, and PKR is activated by CUG-repeat expression in vitro (Tian et al. 2000). Further studies using mouse models; however, indicated that PKR is not crucial to disease pathogenesis. Neither myotonia nor histological changes were altered in HSA250 mice on a PKR-/- or PKR-/+ background, suggesting that PKR is unlikely to be relevant to DM pathogenesis (Mankodi et al. 2003).
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