title: Telomeric repeat silencing in germ cells is essential for early development in Drosophila.
abstract: The germline-specific role of telomeres consists of chromosome end elongation and proper chromosome segregation during early developmental stages. Despite the crucial role of telomeres in germ cells, little is known about telomere biology in the germline. We analyzed telomere homeostasis in the Drosophila female germline and early embryos. A novel germline-specific function of deadenylase complex Ccr4-Not in the telomeric transcript surveillance mechanism is reported. Depletion of Ccr4-Not complex components causes strong derepression of the telomeric retroelement HeT-A in the germ cells, accompanied by elongation of the HeT-A poly(A) tail. Dysfunction of transcription factors Woc and Trf2, as well as RNA-binding protein Ars2, also results in the accumulation of excessively polyadenylated HeT-A transcripts in ovaries. Germline knockdowns of Ccr4-Not components, Woc, Trf2 and Ars2, lead to abnormal mitosis in early embryos, characterized by chromosome missegregation, centrosome dysfunction and spindle multipolarity. Moreover, the observed phenotype is accompanied by the accumulation of HeT-A transcripts around the centrosomes in early embryos, suggesting the putative relationship between overexpression of telomeric transcripts and mitotic defects. Our data demonstrate that Ccr4-Not, Woc, Trf2 and Ars2, components of different regulatory pathways, are required for telomere protection in the germline in order to guarantee normal development.
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Valeriya
authors.initials: V
authors.lastname: Morgunova
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Natalia
authors.initials: N
authors.lastname: Akulenko
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Elizaveta
authors.initials: E
authors.lastname: Radion
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Ivan
authors.initials: I
authors.lastname: Olovnikov
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Abramov
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Ludmila V
authors.initials: LV
authors.lastname: Olenina
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Sergey
authors.initials: S
authors.lastname: Shpiz
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Daria V
authors.initials: DV
authors.lastname: Kopytova
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Sofia G
authors.initials: SG
authors.lastname: Georgieva
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russian Federation allakalm@img.ras.ru.
authors.forename: Alla
authors.initials: A
authors.lastname: Kalmykova
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D008938:Mitosis / Q000235:genetics; D010053:Ovary / Q000378:metabolism; D010063:Ovum / Q000378:metabolism; D026723:Polyadenylation; D016601:RNA-Binding Proteins; D018626:Retroelements; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism; D016615:Telomere; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C568695:NOT1 protein, Drosophila; D016601:RNA-Binding Proteins; D018626:Retroelements; C509085:TRF2 protein, Drosophila; D035341:Telomeric Repeat Binding Protein 2; D014157:Transcription Factors; C414987:WOC protein, Drosophila; C501437:CCR4 protein, Drosophila; D012260:Ribonucleases