Conserved Translatome Remodeling in Nematode Species Executing a Shared Developmental Transition

Nematodes of the genus Caenorhabditis enter a developmental diapause state after hatching in the absence of food. To better understand the relative contributions of distinct regulatory modalities to gene expression changes associated with this developmental transition, we characterized genome-wide changes in mRNA abundance and translational efficiency associated with L1 diapause exit in four species using ribosome profiling and mRNA-seq. We found a strong tendency for translational regulation and mRNA abundance processes to act synergistically, together effecting a dramatic remodeling of the gene expression program. While gene-specific differences were observed between species, overall translational dynamics were broadly and functionally conserved. A striking, conserved feature of the response was strong translational suppression of ribosomal protein production during L1 diapause, followed by activation upon resumed development. On a global scale, ribosome footprint abundance changes showed greater similarity between species than changes in mRNA abundance, illustrating a substantial and genome-wide contribution of translational regulation to evolutionary maintenance of stable gene expression.Author Summary: Working with a set of four related animal species, we have studied a conserved developmental and metabolic transition at the level of protein production and regulation of RNA levels. Strikingly, regulatory effects at the level of RNA accumulation and protein synthesis act together to achieve the observed metabolic shift. In addition to a general conservation of the underlying basis for the regulation of individual genes, alterations of these two processes—mRNA production and protein synthesis—can compensate for one another during evolution to maintain stable amounts of functional gene products. A salient feature of the observed regulation was the storage of idle mRNAs encoding key members of the protein synthesis machinery during metabolic arrest (diapause). Maintenance of this pool facilitates re-activation upon feeding, with the rapid regeneration of protein synthesis capacity an early and critical function during adaptation to a major metabolic shift.