title: RNA-related nuclear functions of human Pat1b, the P-body mRNA decay factor.
abstract: The evolutionarily conserved Pat1 proteins are P-body components recently shown to play important roles in cytoplasmic gene expression control. Using human cell lines, we demonstrate that human Pat1b is a shuttling protein whose nuclear export is mediated via a consensus NES sequence and Crm1, as evidenced by leptomycin B (LMB) treatment. However, not all P-body components are nucleocytoplasmic proteins; rck/p54, Dcp1a, Edc3, Ge-1, and Xrn1 are insensitive to LMB and remain cytoplasmic in its presence. Nuclear Pat1b localizes to PML-associated foci and SC35-containing splicing speckles in a transcription-dependent manner, whereas in the absence of RNA synthesis, Pat1b redistributes to crescent-shaped nucleolar caps. Furthermore, inhibition of splicing by spliceostatin A leads to the reorganization of SC35 speckles, which is closely mirrored by Pat1b, indicating that it may also be involved in splicing processes. Of interest, Pat1b retention in these three nuclear compartments is mediated via distinct regions of the protein. Examination of the nuclear distribution of 4E-T(ransporter), an additional P-body nucleocytoplasmic protein, revealed that 4E-T colocalizes with Pat1b in PML-associated foci but not in nucleolar caps. Taken together, our findings strongly suggest that Pat1b participates in several RNA-related nuclear processes in addition to its multiple regulatory roles in the cytoplasm.
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Aline
authors.initials: A
authors.lastname: Marnef
authors.forename: Dominique
authors.initials: D
authors.lastname: Weil
authors.forename: Nancy
authors.initials: N
authors.lastname: Standart
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D017381:Spliceosomes / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C411571:EIF4ENIF1 protein, human; D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals; D029543:Nucleocytoplasmic Transport Proteins; C526510:PATL1 protein, human; D012333:RNA, Messenger
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