UBL5 is an atypical ubiquitin-like protein, whose function in metazoans remains largely unexplored. We show that UBL5 is required for sister chromatid cohesion maintenance in human cells. UBL5 primarily associates with spliceosomal proteins, and UBL5 depletion decreases pre-mRNA splicing efficiency, leading to globally enhanced intron retention. Defective sister chromatid cohesion is a general consequence of dysfunctional pre-mRNA splicing, resulting from the selective downregulation of the cohesion protection factor Sororin. As the UBL5 yeast orthologue, Hub1, also promotes spliceosome functions, our results show that UBL5 plays an evolutionary conserved role in pre-mRNA splicing, the integrity of which is essential for the fidelity of chromosome segregation.

• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• chromatidy genetika   MeSH
• HeLa buňky MeSH
• lidé MeSH
• ligasy genetika   MeSH
• mitóza genetika   MeSH
• oční proteiny genetika   metabolismus   MeSH
• prekurzory RNA genetika   MeSH
• proteiny buněčného cyklu genetika   MeSH
• regulace genové exprese MeSH
• Saccharomyces cerevisiae - proteiny genetika   MeSH
• segregace chromozomů genetika   MeSH
• sestřih RNA genetika   MeSH
• spliceozomy genetika   MeSH
• ubikvitiny genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Ubiquitin-like 5 (UBL5), which is supposed to be involved in regulation of feed intake, energy metabolism, obesity and type 2 diabetes, is located at position 62.1 cM on the pig chromosome 2 region harbouring quantitative trait loci for carcass and meat quality. The 4,354 bp genomic sequence (FR798948) of the porcine gene encompassing the promoter and entire gene was cloned by polymerase chain reaction. Comparative sequencing revealed 13 polymorphisms in noncoding regions. Synthesis of full-length cDNA sequences using rapid amplification of 5' and 3' ends showed three splice variants. Variants 1 and 2 differ in transcription length for the untranslated part of exon 1 with deduced protein of 73 amino acid (aa) residues and 100 % identities between human, mouse and other species. Variant 3, with 4 bp deletion at the 3' end of exon 2, encodes a truncated protein with 28 aa residues. In a Wild boar×Meishan F2 population (n = 334) with 47 recorded traits, loci FR798948:g.2788G>A and FR798948:g.2141T>C were associated at nominal P < 0.05 with fat deposition, growth and fattening and muscling but after adjustment for multiple testing (Benjamini and Hochberg, J R Stat Soc B 57:289-300, 1995) only eight fat deposition traits showed suggestive association with FR798948:g.2788G>A at adjusted P < 0.10. In a Meishan×Large White (MLW) cross (n = 562) with six trait records available, FR798948:g.2141T>C showed suggestive association with growth (adjusted P = 0.0690). As association mapping conducted in the outbred MLW population is more precise than in the three generation F2 population the UBL5 gene tends to be associated with growth rather than with fat accretion.

• MeSH
• genetické asociační studie * MeSH
• genom * MeSH
• klonování DNA MeSH
• messenger RNA * MeSH
• polymorfismus genetický * MeSH
• pořadí genů MeSH
• prasata genetika   MeSH
• promotorové oblasti (genetika) MeSH
• sestřih RNA * MeSH
• ubikvitiny genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• Nedd8,
• MeSH
• kulinové proteiny MeSH
• lidé MeSH
• posttranslační úpravy proteinů * fyziologie   MeSH
• proteinligasy komplexu SCF MeSH
• ubikvitinace fyziologie   MeSH
• ubikvitiny genetika   MeSH
• Check Tag
• lidé MeSH

UBL5 protein, a structural homologue of ubiquitin, was shown to be involved in pre-mRNA splicing and transcription regulation in yeast and Caenorhabditis elegans, respectively. However, role of the UBL5 human orthologue is still elusive. In our study, we observed that endogenous human UBL5 that was localized in the nucleus, partially associates with Cajal bodies (CBs), nuclear domains where spliceosomal components are assembled. Simultaneous expression of exogenous UBL5 and coilin resulted in their nuclear colocalization in HeLa cells. The ability of UBL5 to interact with coilin was proved by GST pull-down assay using coilin that was either in vitro translated or extracted from HEK293T cells. Further, our results showed that the UBL5-coilin interaction was not influenced by coilin phosphorylation. These results suggest that UBL5 could be targeted to CBs via its interaction with coilin. Relation between human UBL5 protein and CBs is in the agreement with current observations about yeast orthologue Hub1 playing important role in alternative splicing.

• MeSH
• Cajalova tělíska metabolismus   MeSH
• fluorescenční mikroskopie MeSH
• glutathiontransferasa genetika   metabolismus   MeSH
• HEK293 buňky MeSH
• HeLa buňky MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• lidé MeSH
• oční proteiny genetika   metabolismus   MeSH
• rekombinantní fúzní proteiny genetika   metabolismus   MeSH
• transfekce MeSH
• ubikvitiny genetika   metabolismus   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• finanční podpora výzkumu jako téma MeSH
• kardiovaskulární nemoci terapie   MeSH
• lidé MeSH
• posttranslační úpravy proteinů genetika   imunologie   MeSH
• proteasomový endopeptidasový komplex genetika   terapeutické užití   MeSH
• protinádorové látky terapeutické užití   MeSH
• transkripční faktory genetika   terapeutické užití   MeSH
• ubikvitiny genetika   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH