Publication Date:
2017-03-23
Description:
DND1 maintains germline stem cells via recruitment of the CCR4–NOT complex to target mRNAs Nature 543, 7646 (2017). doi:10.1038/nature21690 Authors: Masashi Yamaji, Miki Jishage, Cindy Meyer, Hemant Suryawanshi, Evan Der, Misaki Yamaji, Aitor Garzia, Pavel Morozov, Sudhir Manickavel, Hannah L. McFarland, Robert G. Roeder, Markus Hafner & Thomas Tuschl The vertebrate-conserved RNA-binding protein DND1 is required for the survival of primordial germ cells (PGCs), as well as the suppression of germ cell tumours in mice. Here we show that in mice DND1 binds a UU(A/U) trinucleotide motif predominantly in the 3′ untranslated regions of mRNA, and destabilizes target mRNAs through direct recruitment of the CCR4–NOT deadenylase complex. Transcriptomic analysis reveals that the extent of suppression is dependent on the number of DND1-binding sites. This DND1-dependent mRNA destabilization is required for the survival of mouse PGCs and spermatogonial stem cells by suppressing apoptosis. The spectrum of target RNAs includes positive regulators of apoptosis and inflammation, and modulators of signalling pathways that regulate stem-cell pluripotency, including the TGFβ superfamily, all of which are aberrantly elevated in DND1-deficient PGCs. We propose that the induction of the post-transcriptional suppressor DND1 synergizes with concurrent transcriptional changes to ensure precise developmental transitions during cellular differentiation and maintenance of the germ line.
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
