Human Molecular Genetics, Vol 6, 2117-2126, Copyright © 1997 by Oxford University Press
A Wang, J Forman-Kay, Y Luo, M Luo, YH Chow, J Plumb, JD Friesen, LC Tsui, HH Heng, JL Woolford Jr and J Hu
Nuclear RNA splicing occurs in an RNA-protein complex, termed the
spliceosome. U4/U6 snRNP is one of four essential small nuclear
ribonucleoprotein (snRNP) particles (U1, U2, U5 and U4/U6) present in the
spliceosome. U4/U6 snRNP contains two snRNAs (U4 and U6) and a number of
proteins. We report here the identification and characterization of two
human genes encoding U4/U6-associated splicing factors, Hprp3p and Hprp4p,
respectively. Hprp3p is a 77 kDa protein, which is homologous to the
Saccharomyces cerevisiae splicing factor Prp3p. Amino acid sequence
analysis revealed two putative homologues in Caenorhabditis elegans and
Schizosaccharomyces pombe. Polyclonal antibodies against Hprp3p were
generated with His-tagged Hprp3p over- produced in Escherichia coli . This
splicing factor can co- immunoprecipitate with U4, U6 and U5 snRNAs,
suggesting that it is present in the U4/U6.U5 tri-snRNP. Hprp4p is a 58 kDa
protein homologous to yeast splicing factor Prp4p. Like yeast Prp4p, the
human homologue contains repeats homologous to the beta-subunit of G-
proteins. These repeats are called WD repeats because there is a highly
conserved dipeptide of tryptophan and aspartic acid present at the end of
each repeat. The primary amino acid sequence homology between human Hprp4p
and yeast Prp4p led to the discovery of two additional WD repeats in yeast
Prp4p. Structural homology between these human and yeast splicing factors
and the beta-subunit of G-proteins has been identified by
sequence-similarity comparison and analysis of the protein folding by
threading. Structural models of Hprp4p and Prp4p with a seven-blade
beta-propeller topology have been generated based on the structure of
beta-transducin. Hprp3p and Hprp4p have been shown to interact with each
other and the first 100 amino acids of Hprp3p are not essential for this
interaction. These experiments suggest that both Hprp3p and Hprp4p are
components of human spliceosomes.
ARTICLES
Identification and characterization of human genes encoding Hprp3p and Hprp4p, interacting components of the spliceosome
Division of Respiratory Research, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
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