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-Structure paper
| タイトル | Control of 3' splice site selection by the yeast splicing factor Fyv6. |
|---|---|
| ジャーナル・号・ページ | bioRxiv, Year 2024 |
| 掲載日 | 2024年10月21日 |
著者 | Katherine A Senn / Karli A Lipinski / Natalie J Zeps / Amory F Griffin / Max E Wilkinson / Aaron A Hoskins / ![]() |
| PubMed 要旨 | Pre-mRNA splicing is catalyzed in two steps: 5' splice site (SS) cleavage and exon ligation. A number of proteins transiently associate with spliceosomes to specifically impact these steps (1 and 2 ...Pre-mRNA splicing is catalyzed in two steps: 5' splice site (SS) cleavage and exon ligation. A number of proteins transiently associate with spliceosomes to specifically impact these steps (1 and 2 step factors). We recently identified Fyv6 (FAM192A in humans) as a 2 step factor in ; however, we did not determine how widespread Fyv6's impact is on the transcriptome. To answer this question, we have used RNA-seq to analyze changes in splicing. These results show that loss of Fyv6 results in activation of non-consensus, branch point (BP) proximal 3' SS transcriptome-wide. To identify the molecular basis of these observations, we determined a high-resolution cryo-EM structure of a yeast product complex spliceosome containing Fyv6 at 2.3 Å. The structure reveals that Fyv6 is the only 2 step factor that contacts the Prp22 ATPase and that Fyv6 binding is mutually exclusive with that of the 1 step factor Yju2. We then use this structure to dissect Fyv6 functional domains and interpret results of a genetic screen for suppressor mutations. The combined transcriptomic, structural, and genetic studies allow us to propose a model in which Yju2/Fyv6 exchange facilitates exon ligation and Fyv6 promotes usage of consensus, BP distal 3' SS. |
リンク | bioRxiv / PubMed:38746449 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.31 Å |
| 構造データ | EMDB-47157: Yeast post-catalytic P complex spliceosome, state I, overall map |
| 化合物 | ![]() ChemComp-MG: ![]() ChemComp-K: ![]() ChemComp-IHP: ![]() ChemComp-GTP: ![]() ChemComp-ZN: ![]() ChemComp-HOH: |
| 由来 |
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キーワード | SPLICING / spliceosome / snRNA / yeast / ribonucleoprotein complex |
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