Telomeric repeat silencing in germ cells is essential for early development in Drosophila

Nucleic Acids Res. 2015 Oct 15;43(18):8762-73. doi: 10.1093/nar/gkv775. Epub 2015 Aug 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila / embryology
  • Drosophila / genetics*
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Embryonic Development / genetics
  • Female
  • Gene Expression Regulation, Developmental*
  • Gene Silencing*
  • Mitosis / genetics
  • Ovary / metabolism
  • Ovum / metabolism
  • Polyadenylation
  • RNA-Binding Proteins
  • Retroelements*
  • Ribonucleases / genetics
  • Ribonucleases / metabolism
  • Telomere*
  • Telomeric Repeat Binding Protein 2 / genetics
  • Telomeric Repeat Binding Protein 2 / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • NOT1 protein, Drosophila
  • RNA-Binding Proteins
  • Retroelements
  • TRF2 protein, Drosophila
  • Telomeric Repeat Binding Protein 2
  • Transcription Factors
  • WOC protein, Drosophila
  • CCR4 protein, Drosophila
  • Ribonucleases