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. 2019 Feb 13;47(5):2487–2505. doi: 10.1093/nar/gkz086

Figure 6.

Figure 6.

Proposed roles of TDP-43 in post-transcriptional modifications of U1 and U2 snRNAs via the trafficking of UG-rich motif-bearing C/D scaRNAs to CBs. WDR79 transports H/ACA scaRNAs to CBs via binding to the CAB box of H/ACA scaRNAs that guide site-specific pseudouridylation of snRNA. In contrast, TDP-43 assists with the CB localization of UG-rich motif-bearing C/D scaRNAs (UG-rich C/D scaRNAs), including scaRNA7, scaRNA2, scaRNA9 and scaRNA28. In CBs, scaRNA7 guides the 2′-O-methylation of 70A in U1 snRNA, whereas scaRNAs 2, 9 and 28 guide the 2′-O-methylation of 25G/61C, 19G and 47U in U2 snRNA, respectively. The modified snRNAs (pseudouridylation and 2′-O-methylation are indicated by sky blue stars and red stars, respectively) are incorporated into the spliceosome as U snRNPs to perform the splicing reaction. Depletion of TDP-43 causes de-localization of the CB-localized UG-rich C/D scaRNAs into the nucleolus, resulting in the reduction of the site-specific 2′-O-methylations of U1 and U2 snRNAs.