The multifunctional human p100 protein 'hooks' methylated ligands.
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.
Shaw
Neil
N
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Zhao
Min
M
Cheng
Chongyun
C
Xu
Hao
H
Saarikettu
Juha
J
Li
Yang
Y
Da
Yurong
Y
Yao
Zhi
Z
Silvennoinen
Olli
O
Yang
Jie
J
Liu
Zhi-Jie
ZJ
Wang
Bi-Cheng
BC
Rao
Zihe
Z
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
D008024:Ligands; D009687:Nuclear Proteins; D012322:RNA Precursors; D017411:Ribonucleoproteins, Small Nuclear; D014157:Transcription Factors; D004720:Endonucleases; C095221:SND1 protein, human