title: Transcriptional co-activator protein p100 interacts with snRNP proteins and facilitates the assembly of the spliceosome.
abstract: Transcription and pre-mRNA splicing are the key nuclear processes in eukaryotic gene expression, and identification of factors common to both processes has suggested that they are functionally coordinated. p100 protein has been shown to function as a transcriptional co-activator for several transcription factors. p100 consists of staphylococcal nuclease (SN)-like and Tudor-SN (TSN) domains of which the SN-like domains have been shown to function in transcription, but the function of TSN domain has remained elusive. Here we identified interaction between p100 and small nuclear ribonucleoproteins (snRNP) that function in pre-mRNA splicing. The TSN domain of p100 specifically interacts with components of the U5 snRNP, but also with the other spliceosomal snRNPs. In vitro splicing assays revealed that the purified p100, and specifically the TSN domain of p100, accelerates the kinetics of the spliceosome assembly, particularly the formation of complex A, and the transition from complex A to B. Consistently, the p100 protein, as well as the separated TSN domain, enhanced the kinetics of the first step of splicing in an in vitro splicing assay in dose-dependent manner. Thus our results suggest that p100 protein is a novel dual function regulator of gene expression that participates via distinct domains in both transcription and splicing.
authors.affiliation: Department of Immunology, Tianjin Medical University, Heping District Qixiangtai Road No.22, 300070 Tianjin, PR China. yangj@tijmu.edu.cn
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Tuuli
authors.initials: T
authors.lastname: Välineva
authors.forename: Jingxin
authors.initials: J
authors.lastname: Hong
authors.forename: Tianxu
authors.initials: T
authors.lastname: Bu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.forename: Ole N
authors.initials: ON
authors.lastname: Jensen
authors.forename: Mikko J
authors.initials: MJ
authors.lastname: Frilander
authors.forename: Olli
authors.initials: O
authors.lastname: Silvennoinen
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004720:Endonucleases; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism*; D017415:Ribonucleoprotein, U5 Small Nuclear / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism*; D017381:Spliceosomes / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D017415:Ribonucleoprotein, U5 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; D004720:Endonucleases; C095221:SND1 protein, human