title: WRN helicase accelerates the transcription of ribosomal RNA as a component of an RNA polymerase I-associated complex.
abstract: Werner syndrome (WS) is a rare autosomal recessive genetic disorder causing premature aging. The gene (WRN) responsible for WS encodes a protein homologous to the RecQ-type helicase. WRN has a nucleolar localization signal and shows intranuclear trafficking between the nucleolus and the nucleoplasm. WRN is recruited into the nucleolus when rRNA transcription is reactivated in quiescent cells. Inhibition of mRNA transcription with alpha-amanitin has no effect on nucleolar localization of WRN whereas inhibition of rRNA transcription with actinomycin D releases WRN from nucleoli, suggesting that nucleolar WRN is closely related to rRNA transcription by RNA polymerase I (RPI). A possible function of WRN on rRNA transcription through interaction with RPI is supported by the results described here showing that WRN is co-immunoprecipitated with an RPI subunit, RPA40. Here we show that WS fibroblasts are characterized by a decreased level of rRNA transcription compared with wild-type cells, and that the decreased level of rRNA transcription in WS fibroblasts recovers when wild-type WRN is exogenously expressed. By contrast, exogenously expressed mutant-type WRN lacking an ability to migrate into the nucleolus fails to stimulate rRNA transcription. These results suggest that WRN promotes rRNA transcription as a component of an RPI-associated complex in the nucleolus.
authors.affiliation: AGENE Research Institute, 200 Kajiwara, Kamukura, Kanagawa 247-0063, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Shiratori
authors.forename: Takahisa
authors.initials: T
authors.lastname: Suzuki
authors.forename: Chie
authors.initials: C
authors.lastname: Itoh
authors.forename: Makoto
authors.initials: M
authors.lastname: Goto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Furuichi
authors.forename: Takehisa
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D000546:Amanitins / Q000494:pharmacology; D002460:Cell Line; D002466:Cell Nucleolus / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D004265:DNA Helicases / Q000032:analysis / Q000502:physiology*; D004261:DNA Replication; D003609:Dactinomycin / Q000494:pharmacology; D005090:Exodeoxyribonucleases; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D012318:RNA Polymerase I / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000096:biosynthesis*; D053484:RecQ Helicases; D014158:Transcription, Genetic; D014898:Werner Syndrome / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D000071657:Werner Syndrome Helicase
chemical_list: D000546:Amanitins; D046911:Macromolecular Substances; D019384:Nucleic Acid Synthesis Inhibitors; D012335:RNA, Ribosomal; D003609:Dactinomycin; D012318:RNA Polymerase I; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase