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dc.contributor.authorSalehi, Zivaren
dc.contributor.authorGeffers, Larsen
dc.contributor.authorVilela, Cristinaen
dc.contributor.authorBirkenhäger, Ralfen
dc.contributor.authorPtushkina, Marinaen
dc.contributor.authorBerthelot, Karineen
dc.contributor.authorFerro, Myriamen
dc.contributor.authorGaskell, Simon Jen
dc.contributor.authorHagan, Iain Men
dc.contributor.authorStapley, Benen
dc.contributor.authorMcCarthy, John E Gen
dc.date.accessioned2009-10-16T11:34:25Z
dc.date.available2009-10-16T11:34:25Z
dc.date.issued2002-10
dc.identifier.citationA nuclear protein in Schizosaccharomyces pombe with homology to the human tumour suppressor Fhit has decapping activity. 2002, 46 (1):49-62 Mol. Microbiol.en
dc.identifier.issn0950-382X
dc.identifier.pmid12366830
dc.identifier.doi10.1046/j.1365-2958.2002.03151.x
dc.identifier.urihttp://hdl.handle.net/10541/84341
dc.description.abstractA number of eukaryotic proteins are already known to orchestrate key steps of mRNA metabolism and translation via interactions with the 5' m7GpppN cap. We have characterized a new type of histidine triad (HIT) motif protein (Nhm1) that co-purifies with the cap-binding complex eIF4F of Schizosaccharomyces pombe. Nhm1 is an RNA-binding protein that binds to m7GTP-Sepharose, albeit with lower specificity and affinity for methylated GTP than is typical for the cap-binding protein known as eukaryotic initiation factor 4E. Sequence searches have revealed that proteins with strong sequence similarity over all regions of the new protein exist in a wide range of eukaryotes, yet none has been characterized up to now. However, other proteins that share specific motifs with Nhm1 include the human Fhit tumour suppressor protein and the diadenosine 5', 5"'-P1, P4-tetraphosphate asymmetrical hydrolase of S. pombe. Our experimental work also reveals that Nhm1 inhibits translation in a cell-free extract prepared from S. pombe, and that it is therefore a putative translational modulator. On the other hand, purified Nhm1 manifests mRNA decapping activity, yet is physically distinct from the Saccharomyces cerevisiae decapping enzyme Dcp1. Moreover, fluorescence and immunofluorescence microscopy show that Nhm1 is predominantly, although not exclusively, nuclear. We conclude that Nhm1 has evolved as a special branch of the HIT motif superfamily that has the potential to influence both the metabolism and the translation of mRNA, and that its presence in S. pombe suggests the utilization of a novel decapping pathway.
dc.language.isoenen
dc.subjectTumour Suppressor Genesen
dc.subject.meshAcid Anhydride Hydrolases
dc.subject.meshAmino Acid Sequence
dc.subject.meshGene Expression Regulation, Fungal
dc.subject.meshGenes, Tumor Suppressor
dc.subject.meshMolecular Sequence Data
dc.subject.meshNeoplasm Proteins
dc.subject.meshNuclear Proteins
dc.subject.meshProtein Biosynthesis
dc.subject.meshRNA Caps
dc.subject.meshRNA, Messenger
dc.subject.meshRNA-Binding Proteins
dc.subject.meshSchizosaccharomyces
dc.subject.meshSchizosaccharomyces pombe Proteins
dc.subject.meshSequence Homology, Amino Acid
dc.titleA nuclear protein in Schizosaccharomyces pombe with homology to the human tumour suppressor Fhit has decapping activity.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biomolecular Sciences, UMIST, PO Box 88, Manchester M60 1QD, UK.en
dc.identifier.journalMolecular Microbiologyen
html.description.abstractA number of eukaryotic proteins are already known to orchestrate key steps of mRNA metabolism and translation via interactions with the 5' m7GpppN cap. We have characterized a new type of histidine triad (HIT) motif protein (Nhm1) that co-purifies with the cap-binding complex eIF4F of Schizosaccharomyces pombe. Nhm1 is an RNA-binding protein that binds to m7GTP-Sepharose, albeit with lower specificity and affinity for methylated GTP than is typical for the cap-binding protein known as eukaryotic initiation factor 4E. Sequence searches have revealed that proteins with strong sequence similarity over all regions of the new protein exist in a wide range of eukaryotes, yet none has been characterized up to now. However, other proteins that share specific motifs with Nhm1 include the human Fhit tumour suppressor protein and the diadenosine 5', 5"'-P1, P4-tetraphosphate asymmetrical hydrolase of S. pombe. Our experimental work also reveals that Nhm1 inhibits translation in a cell-free extract prepared from S. pombe, and that it is therefore a putative translational modulator. On the other hand, purified Nhm1 manifests mRNA decapping activity, yet is physically distinct from the Saccharomyces cerevisiae decapping enzyme Dcp1. Moreover, fluorescence and immunofluorescence microscopy show that Nhm1 is predominantly, although not exclusively, nuclear. We conclude that Nhm1 has evolved as a special branch of the HIT motif superfamily that has the potential to influence both the metabolism and the translation of mRNA, and that its presence in S. pombe suggests the utilization of a novel decapping pathway.


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