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  The conserved ubiquitin-like protein Hub1 plays a critical role in splicing in human cells

Ammon, T., Mishra, S. K., Kowalska, K., Popowicz, G. M., Holak, T. A., & Jentsch, S. (2014). The conserved ubiquitin-like protein Hub1 plays a critical role in splicing in human cells. JOURNAL OF MOLECULAR CELL BIOLOGY, 6(4), 312-323. doi:10.1093/jmcb/mju026.

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 Creators:
Ammon, Tim1, Author              
Mishra, Shravan Kumar1, Author              
Kowalska, Kaja2, Author              
Popowicz, Grzegorz M.2, Author              
Holak, Tad A.2, Author              
Jentsch, Stefan1, Author              
Affiliations:
1Jentsch, Stefan / Molecular Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565156              
2Holak, Tad / NMR Spectroscopy, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565154              

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Free keywords: PRE-MESSENGER-RNA; IN-VIVO; NUCLEAR SPECKLES; MAMMALIAN-CELLS; GENE-EXPRESSION; FISSION YEAST; TRI-SNRNP; EXON; SPLICEOSOME; MODIFIERapoptosis; Hub1; splicing; spliceosome; ubiquitin-like proteins;
 Abstract: Different from canonical ubiquitin-like proteins, Hub1 does not form covalent conjugates with substrates but binds proteins non-covalently. In Saccharomyces cerevisiae, Hub1 associates with spliceosomes and mediates alternative splicing of SRC1, without affecting pre-mRNA splicing generally. Human Hub1 is highly similar to its yeast homolog, but its cellular function remains largely unexplored. Here, we show that human Hub1 binds to the spliceosomal protein Snu66 as in yeast; however, unlike its S. cerevisiae homolog, human Hub1 is essential for viability. Prolonged in vivo depletion of human Hub1 leads to various cellular defects, including splicing speckle abnormalities, partial nuclear retention of mRNAs, mitotic catastrophe, and consequently cell death by apoptosis. Early consequences of Hub1 depletion are severe splicing defects, however, only for specific splice sites leading to exon skipping and intron retention. Thus, the ubiquitin-like protein Hub1 is not a canonical spliceosomal factor needed generally for splicing, but rather a modulator of spliceosome performance and facilitator of alternative splicing.

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Language(s): eng - English
 Dates: 2014-08
 Publication Status: Published in print
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000339916900005
DOI: 10.1093/jmcb/mju026
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Title: JOURNAL OF MOLECULAR CELL BIOLOGY
Source Genre: Journal
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Publ. Info: GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND : OXFORD UNIV PRESS
Pages: - Volume / Issue: 6 (4) Sequence Number: - Start / End Page: 312 - 323 Identifier: ISSN: 1674-2788