Crooked neck is a component of the human spliceosome and implicated in the splicing process.
The Drosophila crooked neck (crn) gene is essential for embryogenesis and has been implicated in cell cycle progression and in pre-mRNA splicing although a direct role in either process has not been established. Here we report isolation of the human crooked neck homolog, HCRN, and provide evidence for its function in splicing. HCRN encodes an unusual protein composed largely of tetratricopeptide repeat (TPR) elements. The crooked neck protein co-localizes with the SR and Sm protein splicing factors in discrete subnuclear domains implicated in snRNP biogenesis. In vitro assembly experiments show that an 83 kDa hcrn isoform is stably recruited to splicing complexes coincident with the addition of the U4/U6.U5 tri-snRNP particle. Crooked neck activity appears essential as extracts depleted of hcrn fail to splice pre-mRNA. These and related data support the view that crooked neck is a phylogenetically conserved pre-mRNA splicing factor.
Chung
Seyung
S
T.H. Morgan School of Biological Sciences, University of Kentucky, Lexington, KY 40506, USA.
Zhou
Zhaolan
Z
Huddleston
Kathleen A
KA
Harrison
Douglas A
DA
Reed
Robin
R
Coleman
Timothy A
TA
Rymond
Brian C
BC
D000595:Amino Acid Sequence; D000818:Animals; D002458:Cell Fractionation; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012326:RNA Splicing; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D017381:Spliceosomes / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
C426069:CRNKL1 protein, human; D029721:Drosophila Proteins; D005656:Fungal Proteins; D009687:Nuclear Proteins; D011506:Proteins; C069204:crn protein, Drosophila