title: Involvement of telomerase reverse transcriptase in heterochromatin maintenance.
abstract: In the fission yeast Schizosaccharomyces pombe, centromeric heterochromatin is maintained by an RNA-directed RNA polymerase complex (RDRC) and the RNA-induced transcriptional silencing (RITS) complex in a manner that depends on the generation of short interfering RNA. In association with the telomerase RNA component (TERC), the telomerase reverse transcriptase (TERT) forms telomerase and counteracts telomere attrition, and without TERC, TERT has been implicated in the regulation of heterochromatin at locations distinct from telomeres. Here, we describe a complex composed of human TERT (hTERT), Brahma-related gene 1 (BRG1), and nucleostemin (NS) that contributes to heterochromatin maintenance at centromeres and transposons. This complex produced double-stranded RNAs homologous to centromeric alpha-satellite (alphoid) repeat elements and transposons that were processed into small interfering RNAs targeted to these heterochromatic regions. These small interfering RNAs promoted heterochromatin assembly and mitotic progression in a manner dependent on the RNA interference machinery. These observations implicate the hTERT/BRG1/NS (TBN) complex in heterochromatin assembly at particular sites in the mammalian genome.
authors.affiliation: Division of Cancer Stem Cell, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Maida
authors.forename: Mami
authors.initials: M
authors.lastname: Yasukawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Okamoto
authors.forename: Seii
authors.initials: S
authors.lastname: Ohka
authors.forename: Keita
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Totoki
authors.forename: Takashi K
authors.initials: TK
authors.lastname: Ito
authors.forename: Tohru
authors.initials: T
authors.lastname: Minamino
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Satoko
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shibata
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Masutomi
mesh_terms: D002460:Cell Line; D002503:Centromere / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006570:Heterochromatin / Q000378:metabolism*; D006801:Humans; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D018626:Retroelements; D012568:Schizosaccharomyces / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D019098:Telomerase / Q000032:analysis / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C469949:GNL3 protein, human; D006570:Heterochromatin; D009687:Nuclear Proteins; D018626:Retroelements; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C509188:trt1 protein, S pombe; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase; D019204:GTP-Binding Proteins; C084108:SMARCA4 protein, human; D004265:DNA Helicases