Publication: Error-Prone Splicing Controlled by the Ubiquitin Relative Hub1
Issued Date
2017-08-03
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ISSN
10974164
10972765
10972765
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2-s2.0-85023635576
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Mahidol University
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SCOPUS
Bibliographic Citation
Molecular Cell. Vol.67, No.3 (2017), 423-432.e4
Suggested Citation
Ramazan Karaduman, Sittinan Chanarat, Boris Pfander, Stefan Jentsch Error-Prone Splicing Controlled by the Ubiquitin Relative Hub1. Molecular Cell. Vol.67, No.3 (2017), 423-432.e4. doi:10.1016/j.molcel.2017.06.021 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41807
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Title
Error-Prone Splicing Controlled by the Ubiquitin Relative Hub1
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Abstract
© 2017 Elsevier Inc. Accurate pre-mRNA splicing is needed for correct gene expression and relies on faithful splice site recognition. Here, we show that the ubiquitin-like protein Hub1 binds to the DEAD-box helicase Prp5, a key regulator of early spliceosome assembly, and stimulates its ATPase activity thereby enhancing splicing and relaxing fidelity. High Hub1 levels enhance splicing efficiency but also cause missplicing by tolerating suboptimal splice sites and branchpoint sequences. Notably, Prp5 itself is regulated by a Hub1-dependent negative feedback loop. Since Hub1-mediated splicing activation induces cryptic splicing of Prp5, it also represses Prp5 protein levels and thus curbs excessive missplicing. Our findings indicate that Hub1 mediates enhanced, but error-prone splicing, a mechanism that is tightly controlled by a feedback loop of PRP5 cryptic splicing activation.