TY - JOUR
T1 - NANOS2 is a sequence-specific mRNA-binding protein that promotes transcript degradation in spermatogonial stem cells
AU - Codino, Azzurra
AU - Turowski, Tomasz
AU - Van De Lagemaat, Louie N.
AU - Ivanova, Ivayla
AU - Tavosanis, Andrea
AU - Much, Christian
AU - Auchynnikava, Tania
AU - Vasiliauskaitė, Lina
AU - Morgan, Marcos
AU - Rappsilber, Juri
AU - Allshire, Robin C.
AU - Kranc, Kamil R.
AU - Tollervey, David
AU - O'carroll, Dónal
PY - 2021/7/23
Y1 - 2021/7/23
N2 - 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.
AB - 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.
U2 - 10.1016/j.isci.2021.102762
DO - 10.1016/j.isci.2021.102762
M3 - Article
SN - 2589-0042
VL - 24
SP - 102762
JO - iScience
JF - iScience
IS - 7
ER -