Nucleic Acids Research, Vol 25, Issue 4 15-23, Copyright © 1997 by Oxford University Press
SE Applequist, M Selg, C Raman, and HM ck
Levels of most nonsense mRNAs are normally reduced in prokaryotes and
eukaryotes when compared with that of corresponding functional mRNAs. Genes
encoding polypeptides that selectively reduce levels of nonsense mRNA have
so far only been identified in simple eukaryotes. We have now cloned a
human cDNA whose deduced amino acid sequence shows the highest degree of
homology to that of UPF1, abona fideSaccharomycescerevisiaegroup I RNA
helicase required for accelerated degradation of nonsense mRNA. Based on
the total sequence of the shorter yeast UPF1 protein, the overall identity
between the human protein and UPF1 is 51%. Besides NTPase and other RNA
helicase consensus motifs, UPF1 and its human homolog also share similar
putative zinc finger motifs that are absent in other group I RNA helicases.
Northern blot analysis with the human cDNA probe revealed two transcripts
in several human cell lines. Further, antibodies raised against a synthetic
peptide of the human polypeptide detected a single 130 kDa polypeptide on
Western blots from human and mouse cells. Finally, immunofluorescence and
Western blot analyses revealed that the human and mouse polypeptides, like
yeast UPF1, are expressed in the cytoplasm, but not in the nucleus. We have
thus identified the first mammalian homolog of yeast UPF1, a protein that
regulates levels of nonsense mRNA, and we tentatively name this protein
human HUPF1 (for humanhomolog ofUPF1).
ARTICLES
Cloning and characterization of HUPF1, a human homolog of the Saccharomyces cerevisiae nonsense mRNA-reducing UPF1 protein
Department of Microbiology and Immunology and Program in Molecular Biology, Stritch School of Medicine, Loyola University of Chicago, Maywood , IL 60153, USA and 1 Hospital for Special Surgery, Cornell University, New York , NY 10021, USA
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