Dauer quiescence as well as continuity of the life cycle after dauer-exit in Caenorhabditis elegans are dependent on the endoribonuclease activity of XRN-2

AbstractCaenorhabditis elegans embarks on a quiescent dauer state upon exposure to unfavourable conditions and can sustain for a very long period without food, but it returns to continuous life cycle upon arrival of suitable conditions. Thus, dauer state plays a critical role in its adaptive fitness and survival. ATP-independent endoribonuclease activity of XRN-2 has been implicated in dauer microRNA metabolism, perturbation of which causes their collapse within a very short span of time. Here, we present a detailed comparative analyses of dauer transcriptomes from a conditional mutant strain for the endoribonuclease activity of XRN-2, maintained under control and experimental conditions. We observed that even a limited disruption of microRNA homeostasis in experimental dauers results in deregulation of a large number of mRNA targets. Our bioinformatic analyses, supported by morphological, physiological, and behavioral evidence further demonstrate critical changes in metabolism leading to a state unsupportive of dauer maintenance, alongside potential defects in multiple neuronal activities, which might have caused an overall disruption of dauer plasticity. We explore a possible role of this endoribonuclease activity towards the maintenance of chromatin architecture and transposon expression that in turn might affect the transcriptional program critically required for the maintenance of non-aging, long-lived dauers. Finally, we also demonstrate that perturbation of the endoribonuclease activity during the dauer state exerts drastic adverse effects on the continuity of life cycle after dauer-exit. They not only fail to recapitulate the wild type events of germline development and embryogenesis, but also present traits of very old worms and formation of ‘tumor-like’ structures in the proximal gonad.