title: A role for the Cajal-body-associated SUMO isopeptidase USPL1 in snRNA transcription mediated by RNA polymerase II.
abstract: Cajal bodies are nuclear structures that are involved in biogenesis of snRNPs and snoRNPs, maintenance of telomeres and processing of histone mRNA. Recently, the SUMO isopeptidase USPL1 was identified as a component of Cajal bodies that is essential for cellular growth and Cajal body integrity. However, a cellular function for USPL1 is so far unknown. Here, we use RNAi-mediated knockdown in human cells in combination with biochemical and fluorescence microscopy approaches to investigate the function of USPL1 and its link to Cajal bodies. We demonstrate that levels of snRNAs transcribed by RNA polymerase (RNAP) II are reduced upon knockdown of USPL1 and that downstream processes such as snRNP assembly and pre-mRNA splicing are compromised. Importantly, we find that USPL1 associates directly with U snRNA loci and that it interacts and colocalises with components of the Little Elongation Complex, which is involved in RNAPII-mediated snRNA transcription. Thus, our data indicate that USPL1 plays a key role in RNAPII-mediated snRNA transcription.
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD15EH, UK.
authors.forename: Saskia
authors.initials: S
authors.lastname: Hutten
authors.forename: Georgia
authors.initials: G
authors.lastname: Chachami
authors.forename: Ulrike
authors.initials: U
authors.lastname: Winter
authors.forename: Frauke
authors.initials: F
authors.lastname: Melchior
authors.forename: Angus I
authors.initials: AI
authors.lastname: Lamond
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D020541:Coiled Bodies; D010450:Endopeptidases / Q000502:physiology*; D056426:Genetic Loci; D057809:HEK293 Cells; D006801:Humans; D055503:Protein Multimerization; D021381:Protein Transport; D012319:RNA Polymerase II / Q000502:physiology*; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D012342:RNA, Small Nuclear / Q000235:genetics* / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D012322:RNA Precursors; D012342:RNA, Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; D012319:RNA Polymerase II; D010450:Endopeptidases; C000592698:USPL1 protein, human
keywords: Cajal body; SUMO isopeptidase; snRNA transcription