دورية أكاديمية
Identification of a small molecule inhibitor that stalls splicing at an early step of spliceosome activation
| العنوان: | Identification of a small molecule inhibitor that stalls splicing at an early step of spliceosome activation |
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| المؤلفون: | Anzhalika Sidarovich, Cindy L Will, Maria M Anokhina, Javier Ceballos, Sonja Sievers, Dmitry E Agafonov, Timur Samatov, Penghui Bao, Berthold Kastner, Henning Urlaub, Herbert Waldmann, Reinhard Lührmann |
| المصدر: | eLife, Vol 6 (2017) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2017. |
| سنة النشر: | 2017 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | spliceosome, pre-mRNA splicing, small molecule inhibitor, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Small molecule inhibitors of pre-mRNA splicing are important tools for identifying new spliceosome assembly intermediates, allowing a finer dissection of spliceosome dynamics and function. Here, we identified a small molecule that inhibits human pre-mRNA splicing at an intermediate stage during conversion of pre-catalytic spliceosomal B complexes into activated Bact complexes. Characterization of the stalled complexes (designated B028) revealed that U4/U6 snRNP proteins are released during activation before the U6 Lsm and B-specific proteins, and before recruitment and/or stable incorporation of Prp19/CDC5L complex and other Bact complex proteins. The U2/U6 RNA network in B028 complexes differs from that of the Bact complex, consistent with the idea that the catalytic RNA core forms stepwise during the B to Bact transition and is likely stabilized by the Prp19/CDC5L complex and related proteins. Taken together, our data provide new insights into the RNP rearrangements and extensive exchange of proteins that occurs during spliceosome activation. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/23533; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.23533 |
| URL الوصول: | https://doaj.org/article/db1e5a6f34b4401e948028326c4304a0 |
| رقم الأكسشن: | edsdoj.b1e5a6f34b4401e948028326c4304a0 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.23533 |