File:Ijms-24-11939-g008-550.webp
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[edit]DescriptionIjms-24-11939-g008-550.webp |
English: Figure 8. Mechanism of action of risdiplam. According to studies in which risdiplam analogues were used, risdiplam may act on two regions of SMN2 exon 7 for highly selective pre-mRNA splicing [147,148]. The first region is the 5′-splice site of exon 7 (TSL2) of the pre-mRNA transcribed from SMN2. A risdiplam molecule stabilizes the duplex of the 5′-splice site RNA sequence and the U1 snRNP RNA sequence and promotes splicing initiation. The second region is the internal structure around exonic splicing enhancer 2 (ESE2) within SMN2 exon 7. A risdiplam molecule binds to the ESE2 region, which alters the stem-loop structure (TSL1) in the first half of SMN2 exon 7. The risdiplam molecule bound to the ESE2 region inhibits hnRNPG protein binding while promoting the binding of two splicing regulatory proteins: far upstream element binding protein 1 (FUBP1) and its homolog, KH-type splicing regulatory protein (KHSRP). TSL1 includes a cis-acting element that suppresses SMN2 exon 7 splicing, and FUBP1 and KHSRP proteins are trans-acting factors that promote SMN2 exon 7 splicing. |
Date | |
Source | https://www.mdpi.com/1422-0067/24/15/11939 |
Author | Nishio, H.; Niba, E.T.E.; Saito, T.; Okamoto, K.; Takeshima, Y.; Awano, H |
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current | 18:33, 16 March 2024 | 550 × 284 (22 KB) | Ozzie10aaaa (talk | contribs) | Uploaded a work by Nishio, H.; Niba, E.T.E.; Saito, T.; Okamoto, K.; Takeshima, Y.; Awano, H from https://www.mdpi.com/1422-0067/24/15/11939 with UploadWizard |
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