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

Ammon T, Mishra SK, Kowalska K, Popowicz GM, Holak TA, Jentsch S
J Mol Cell Biol 6 312-23 (2014)
Cited: 20 times
EuropePMC logo PMID: 24872507

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.

Reviews - 4pyu mentioned but not cited (1)

  1. UBL5/Hub1: An Atypical Ubiquitin-Like Protein with a Typical Role as a Stress-Responsive Regulator. Chanarat S. Int J Mol Sci 22 9384 (2021)

Articles - 4pyu mentioned but not cited (1)

  1. The conserved ubiquitin-like protein Hub1 plays a critical role in splicing in human cells. Ammon T, Mishra SK, Kowalska K, Popowicz GM, Holak TA, Jentsch S. J Mol Cell Biol 6 312-323 (2014)


Reviews citing this publication (4)

  1. Intron specificity in pre-mRNA splicing. Mishra SK, Thakran P. Curr Genet 64 777-784 (2018)
  2. Regulation of Pre-mRNA Splicing: Indispensable Role of Post-Translational Modifications of Splicing Factors. Kretova M, Selicky T, Cipakova I, Cipak L. Life (Basel) 13 604 (2023)
  3. The Ubiquitin-like Proteins of Saccharomyces cerevisiae. Sengupta S, Pick E. Biomolecules 13 734 (2023)
  4. Ubiquitination and Ubiquitin-Like Modifications as Mediators of Alternative Pre-mRNA Splicing in Arabidopsis thaliana. Lan W, Qiu Y, Xu Y, Liu Y, Miao Y. Front Plant Sci 13 869870 (2022)

Articles citing this publication (14)

  1. Structures of the human pre-catalytic spliceosome and its precursor spliceosome. Zhan X, Zhan X, Yan C, Zhang X, Lei J, Shi Y. Cell Res 28 1129-1140 (2018)
  2. An Rtf2 Domain-Containing Protein Influences Pre-mRNA Splicing and Is Essential for Embryonic Development in Arabidopsis thaliana. Sasaki T, Kanno T, Liang SC, Chen PY, Liao WW, Lin WD, Matzke AJ, Matzke M. Genetics 200 523-535 (2015)
  3. Sde2 is an intron-specific pre-mRNA splicing regulator activated by ubiquitin-like processing. Thakran P, Pandit PA, Datta S, Kolathur KK, Pleiss JA, Mishra SK. EMBO J 37 89-101 (2018)
  4. Ubiquitin-Like protein 5 interacts with the silencing suppressor p3 of rice stripe virus and mediates its degradation through the 26S proteasome pathway. Chen B, Lin L, Lu Y, Peng J, Zheng H, Yang Q, Rao S, Wu G, Li J, Chen Z, Song B, Chen J, Yan F. PLoS Pathog 16 e1008780 (2020)
  5. Error-Prone Splicing Controlled by the Ubiquitin Relative Hub1. Karaduman R, Chanarat S, Pfander B, Jentsch S. Mol Cell 67 423-432.e4 (2017)
  6. Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway. Oka Y, Bekker-Jensen S, Mailand N. EMBO J 34 1385-1398 (2015)
  7. Targeting the spliceosome for cutaneous squamous cell carcinoma therapy: a role for c-MYC and wild-type p53 in determining the degree of tumour selectivity. Hepburn LA, McHugh A, Fernandes K, Boag G, Proby CM, Leigh IM, Saville MK. Oncotarget 9 23029-23046 (2018)
  8. Human MFAP1 is a cryptic ortholog of the Saccharomyces cerevisiae Spp381 splicing factor. Ulrich AK, Wahl MC. BMC Evol Biol 17 91 (2017)
  9. AtUBL5 regulates growth and development through pre-mRNA splicing in Arabidopsis thaliana. Watanabe E, Mano S, Nishimura M, Yamada K. PLoS One 14 e0224795 (2019)
  10. Identification of Sugarcane Host Factors Interacting with the 6K2 Protein of the Sugarcane Mosaic Virus. Zhang H, Cheng G, Yang Z, Wang T, Xu J. Int J Mol Sci 20 E3867 (2019)
  11. Broader roles of the ubiquitin-like protein Hub1 indicated by its yeast two-hybrid interactors. Varikkapulakkal A, Ghosh A, Mishra SK. MicroPubl Biol 2022 (2022)
  12. Computer- and NMR-Aided Design of Small-Molecule Inhibitors of the Hub1 Protein. Reyes Romero A, Kubica K, Kitel R, Rodríguez I, Magiera-Mularz K, Dömling A, Holak TA, Surmiak E. Molecules 27 8282 (2022)
  13. Splicing of branchpoint-distant exons is promoted by Cactin, Tls1 and the ubiquitin-fold-activated Sde2. Anil AT, Choudhary K, Pandian R, Gupta P, Thakran P, Singh A, Sharma M, Mishra SK. Nucleic Acids Res 50 10000-10014 (2022)
  14. Ubiquitin-like protein 5 is a novel player in the UPR-PERK arm and ER stress-induced cell death. Wang W, Hawkridge AM, Ma Y, Zhang B, Mangrum JB, Hassan ZH, He T, Blat S, Guo C, Zhou H, Liu J, Wang XY, Fang X. J Biol Chem 299 104915 (2023)


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