Journal
JOURNAL OF MOLECULAR CELL BIOLOGY
Volume 6, Issue 4, Pages 312-323Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jmcb/mju026
Keywords
apoptosis; Hub1; splicing; spliceosome; ubiquitin-like proteins
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Funding
- Max Planck Society
- Louis-Jeantet Foundation
- Deutsche Forschungsgemeinschaft [SPP1365]
- Centre for Integrated Protein Science Munich
- Fonds der chemischen Industrie
- Marie Curie FP7-Reintegration-Grant within 7th European Community Framework Program
- EU European Regional Development Fund
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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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