Pnrc2 promotes rapid mRNA decay and coordinately supports early development with P-body factors Ddx6 and Ddx61

Somitogenesis, the sequential segmentation of vertebrate embryonic mesoderm, is controlled by the segmentation clock, a molecular oscillator that controls periodic gene expression in unsegmented mesoderm and is regulated by a negative feedback loop driven by Hes/Her transcriptional repressors. In zebrafish, Pnrc2 is required for decay of her1 transcript and additional oscillatory gene transcripts. Despite accumulation of numerous mRNAs including those encoding key developmental regulators, overt embryonic phenotypes are absent in pnrc2 mutants. Our previous work suggested that accumulated mRNAs are not translated in pnrc2 mutants, though the underlying mechanism(s) was unknown. We show here that many overexpressed transcripts in pnrc2 mutants have shortened poly(A) tails and are disengaged from ribosomes, and that deadenylation inhibition leads to somite defects in pnrc2 mutants. In contrast, transcripts encoding the P-body protein, Ddx61, are both overexpressed and engaged with ribosomes, leading to an increase in Ddx61 protein. Co-depletion of Ddx61 and its ohnolog Ddx6 enhances her1 accumulation and later leads to strong morphological defects in pnrc2 mutants. Together, our results show that multiple post-transcriptional mechanisms ensure proper translation when mRNA decay is inhibited. Summary statementPnrc2 promotes decay of tail-shortened, ribosome-disengaged mRNAs and co-regulates her1 mRNA decay with Ddx6 and Ddx61, P-body factors that sustain normal development in decay-deficient pnrc2 mutants.