Abstract
In response to adverse environmental cues, Caenorhabditis elegans larvae can temporarily arrest development at the second moult and form dauers, a diapause stage that allows for long-term survival. This process is largely regulated by certain evolutionarily conserved signal transduction pathways, but it is also affected by miRNA-mediated post-transcriptional control of gene expression. The 5′–3′ mRNA decay mechanism contributes to miRNA-mediated silencing of target mRNAs in many organisms but how it affects developmental decisions during normal or stress conditions is largely unknown. Here, we show that loss of the mRNA decapping complex activity acting in the 5′–3′ mRNA decay pathway inhibits dauer formation at the stressful high temperature of 27.5°C, and instead promotes early developmental arrest. Our genetic data suggest that this arrest phenotype correlates with dysregulation of heterochronic gene expression and an aberrant stabilization of lin-14 mRNA at early larval stages. Restoration of neuronal dcap-1 activity was sufficient to rescue growth phenotypes of dcap-1 mutants at both high and normal temperatures, implying the involvement of common developmental timing mechanisms. Our work unveils the crucial role of 5′–3′ mRNA degradation in proper regulation of heterochronic gene expression programmes, which proved to be essential for survival under stressful conditions.
Highlights
Under adverse environmental conditions, survival of an organism depends on the induction of specific developmental programmes able to arrest metabolism and growth in a reversible manner
We observed that the dcap-1 mutation greatly enhances dauer arrest of daf-7(e1372) mutants at the permissive temperature of 158C, forming approximately 65% dauers versus approximately 20% of the single daf-7(e1372) mutants. daf-7 encodes a transforming growth factor-b (TGF-b)-related ligand of the homonymous signalling pathway, which seems to regulate dauer formation in parallel to the insulin/IGF-1 signalling (IIS) pathway [42]
Because miRNA-induced destabilization of mRNA targets is catalysed by enzymes involved in the 50-30 mRNA decay pathway, we presume that high levels of LIN-14 owing to impaired degradation of its mRNA in the decapping mutants, could interfere with the developmental decision that needs to be made by early larvae at high temperature, in order to enter the dauer stage or proceed to later developmental stages
Summary
Survival of an organism depends on the induction of specific developmental programmes able to arrest metabolism and growth in a reversible manner. They enhance dauer formation of dauer-constitutive mutants at permissive temperatures, were shown to prevent entry of wild-type worms in the 2 dauer stage at 27.58C, inducing a prior and irreversible developmental arrest that precludes survival of the organism. This arrest phenotype of decapping mutants is mainly independent of the major dauer signalling pathways, it is partially suppressed by loss of daf-16. Our study unveils a specific role of the mRNA decapping complex in ensuring robust execution of heterochronic gene expression programmes upon environmental perturbations, with a great impact on organismal physiology and survival
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