NANOS2 is a sequence-specific mRNA-binding protein that promotes transcript degradation in spermatogonial stem cells

iScience

Andrea Tavosanis¹  Marcos Morgan²  Christian Much²  Tomasz Turowski³  Tania Auchynnikava⁴  David Tollervey⁴  Ivayla Ivanova⁴  Azzurra Codino⁴  Juri Rappsilber⁴  Kamil R. Kranc⁴  Lina Vasiliauskaitė⁵  Dónal O'Carroll⁶  Robin C. Allshire⁶  Louie N. van de Lagemaat⁶ 

[1] Laboratory of Haematopoietic Stem Cell &Leukaemia Biology, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK;Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK;Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK;;Laboratory of Haematopoietic Stem Cell &Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK;

关键词: Biological sciences;    Molecular biology;    Developmental biology;    Omics;    Transcriptomics;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Spermatogonial stem cells (SSCs) sustain spermatogenesis and fertility throughout adult male life. The conserved RNA-binding protein NANOS2 is essential for the maintenance of SSCs, but its targets and mechanisms of function are not fully understood. Here, we generated a fully functional epitope-tagged Nanos2 mouse allele and applied the highly stringent cross-linking and analysis of cDNAs to define NANOS2 RNA occupancy in SSC lines. NANOS2 recognizes the AUKAAWU consensus motif, mostly found in the 3′ untranslated region of defined messenger RNAs (mRNAs). We find that NANOS2 is a regulator of key signaling and metabolic pathways whose dosage or activity are known to be critical for SSC maintenance. NANOS2 interacts with components of CCR4-NOT deadenylase complex in SSC lines, and consequently, NANOS2 binding reduces the half-lives of target transcripts. In summary, NANOS2 contributes to SSC maintenance through the regulation of target mRNA stability and key self-renewal pathways.

【 授权许可】

Unknown