TDP- Sample Clauses

TDP-. 43 and its interacting RNA binding proteins Several RNA-binding proteins that regulate RNA metabolism show extensive interaction with TDP-43 (Xxxxxxxx et al., 2010; Xxxx et al., 2010). Some of the splicing factors interacting with TDP-43 depend on the N-terminal RRM1 to mediate RNA-protein functions of TDP-43 (Xxxxxxxx et al., 2010). The interactions of TDP-43 with splicing factors are in two distinct clusters: • A nuclear/splicing cluster. A group of nuclear proteins that control RNA splicing as well as other nuclear RNA metabolism were found in this cluster. They include many hnRNPs, SR proteins, snRNPs, and nuclear RNA export factors. These proteins are all implicated in nuclear RNA metabolism (mainly RNA splicing and mRNA export to the cytoplasm) (Xxxxxxxx et al., 2010; Xxxx et al., 2010). • A cytoplasmic/translation cluster. This includes a group of cytoplasmic proteins that regulate mRNA translation. Members of this cluster include translation initiation and elongation factors (Xxxxxxxx et al., 2010). This is in accordance with the suggestion that TDP-43 has numerous functions in RNA metabolism in the nucleus and cytoplasm. Proteins interacting with TDP-43 include some members of CELF proteins and SR proteins family (Xxxxxxxx et al., 2010 660). These splicing factors may be under the influence of TDP-43 to mediate activities other than splicing such as control of mRNA export, localisation and stabilisation. Two members of the SR family of proteins were found in the nuclear splicing cluster of TDP-43 including 9G8 and SRp55 (Xxxxxxxx et al., 2010). However, the only CELF protein identified as an interactor of TDP-43 is CELF1 (Xxxx et al., 2010); (Xxxxxxxx et al., 2010). TDP-43 (like CELF2) regulates CFTR exon 9 skipping by binding an ISE motif at the end of intron 8 (Xxxxxxxx et al., 2010). Whilst CELF1 binds to this same ISE motif, it does not promote CFTR exon 9 skipping (Xxxxxxxx et al., 2010). There are potential similarities between DM1 and TDP-43 proteinopathies. In TDP-43 proteinopathies, TDP-43 is sequestered into cytoplasmic aggregates in neurons while in DM1, there is gain of function of splicing factors (CELF1) in the nucleus. In both diseases, the splicing pattern of their downstream pre-mRNA targets is altered. Although, the exact relationship between mis-splicing of mRNA targets and neurodegeneration in DM1 is not known; it is plausible that in TDP-43 proteinopathies (such as AD with TDP-43 pathology), RNA-binding proteins may be sequest...