ArticleScientific reports2017
Alternative exon skipping biases substrate preference of the deubiquitylase USP15 for mysterin/RNF213, the moyamoya disease susceptibility factor.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- The function of alternative splicing in the proteome: rewiring protein interactomes to put old functions into new contexts.Nature structural & molecular biology · 2023Review
- USP15 in Cancer and Other Diseases: From Diverse Functionsto Therapeutic Targets.Biomedicines · 2022Review
- The Multifaceted Roles of USP15 in Signal Transduction.International journal of molecular sciences · 2021Review
- Global alternative splicing landscape of skeletal muscle atrophy induced by hindlimb unloading.Annals of translational medicine · 2021Article
- The ring finger protein 213 gene (Rnf213) contributes to Rift Valley fever resistance in mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2021Article
- USP15 Deubiquitinates TUT1 Associated with RNA Metabolism and Maintains Cerebellar Homeostasis.Molecular and cellular biology · 2020Article
- ALKBH5 regulates anti-PD-1 therapy response by modulating lactate and suppressive immune cell accumulation in tumor microenvironment.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The AAA+ ATPase/ubiquitin ligase mysterin stabilizes cytoplasmic lipid droplets.The Journal of cell biology · 2019Article
- The deubiquitylase USP15 regulates topoisomerase II alpha to maintain genome integrity.Oncogene · 2018Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The deubiquitylating enzyme USP15 plays significant roles in multiple cellular pathways including TGF-β signaling, RNA splicing, and innate immunity. Evolutionarily conserved skipping of exon 7 occurs during transcription of the mRNAs encoding USP15 and its paralogue USP4, yielding two major isoforms for each gene. Exon 7 of USP15 encodes a serine-rich stretch of 29 amino acid residues located in the inter-region linker that connects the N-terminal putative regulatory region and the C-terminal enzymatic region. Previous findings suggested that the variation in the linker region leads to functional differences between the isoforms of the two deubiquitylating enzymes, but to date no direct evidence regarding such functional divergence has been published. We found that the long isoform of USP15 predominantly recognizes and deubiquitylates mysterin, a large ubiquitin ligase associated with the onset of moyamoya disease. This observation represents the first experimental evidence that the conserved exon skipping alters the substrate specificity of this class of deubiquitylating enzymes. In addition, we found that the interactomes of the short and long isoforms of USP15 only partially overlapped. Thus, USP15, a key gene in multiple cellular processes, generates two functionally different isoforms via evolutionarily conserved exon skipping.
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