title: The multifunctional human p100 protein 'hooks' methylated ligands.
abstract: The human p100 protein is a vital transcription regulator that increases gene transcription by forming a physical bridge between promoter-specific activators and the basal transcription machinery. Here we demonstrate that the tudor and SN (TSN) domain of p100 interacts with U small nuclear ribonucleoprotein (snRNP) complexes, suggesting a role for p100 in the processing of precursor messenger RNA. We determined the crystal structure of the p100 TSN domain to delineate the molecular basis of p100's proposed functions. The interdigitated structure resembles a hook, with a hinge controlling the movement and orientation of the hook. Our studies suggest that a conserved aromatic cage hooks methyl groups of snRNPs and anchors p100 to the spliceosome. These structural insights partly explain the distinct roles of p100 in transcription and splicing.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Neil
authors.initials: N
authors.lastname: Shaw
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Chongyun
authors.initials: C
authors.lastname: Cheng
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Juha
authors.initials: J
authors.lastname: Saarikettu
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Yurong
authors.initials: Y
authors.lastname: Da
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.forename: Olli
authors.initials: O
authors.lastname: Silvennoinen
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Liu
authors.forename: Bi-Cheng
authors.initials: BC
authors.lastname: Wang
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D000595:Amino Acid Sequence; D004720:Endonucleases; D006801:Humans; D008024:Ligands; D008745:Methylation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D017434:Protein Structure, Tertiary; D012322:RNA Precursors / Q000737:chemistry / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism / Q000502:physiology; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology
chemical_list: D008024:Ligands; D009687:Nuclear Proteins; D012322:RNA Precursors; D017411:Ribonucleoproteins, Small Nuclear; D014157:Transcription Factors; D004720:Endonucleases; C095221:SND1 protein, human