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  Smu1 and RED are required for activation of spliceosomal B complexes assembled on short introns.

Keiper, S. M., Papasaikas, P., Will, C. L., Valcárcel, J., Girard, C., & Lührmann, R. (2019). Smu1 and RED are required for activation of spliceosomal B complexes assembled on short introns. Nature Communications, 10(1): 3639. doi:10.1038/s41467-019-11293-8.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0004-7738-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0004-773F-1
Genre: Journal Article

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 Creators:
Keiper, S. M.1, Author              
Papasaikas, P., Author
Will, C. L.1, Author              
Valcárcel, J., Author
Girard, C.1, Author              
Lührmann, R.1, Author              
Affiliations:
1Department of Cellular Biochemistry, MPI for Biophysical Chemistry, Max Planck Society, ou_578576              

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 Abstract: Human pre-catalytic spliceosomes contain several proteins that associate transiently just prior to spliceosome activation and are absent in yeast, suggesting that this critical step is more complex in higher eukaryotes. We demonstrate via RNAi coupled with RNA-Seq that two of these human-specific proteins, Smu1 and RED, function both as alternative splicing regulators and as general splicing factors and are required predominantly for efficient splicing of short introns. In vitro splicing assays reveal that Smu1 and RED promote spliceosome activation, and are essential for this step when the distance between the pre-mRNA's 5' splice site (SS) and branch site (BS) is sufficiently short. This Smu1-RED requirement can be bypassed when the 5' and 3' regions of short introns are physically separated. Our observations suggest that Smu1 and RED relieve physical constraints arising from a short 5'SS-BS distance, thereby enabling spliceosomes to overcome structural challenges associated with the splicing of short introns.

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Language(s): eng - English
 Dates: 2019-08-13
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.1038/s41467-019-11293-8
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Title: Nature Communications
Source Genre: Journal
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Pages: 15 Volume / Issue: 10 (1) Sequence Number: 3639 Start / End Page: - Identifier: -