Conserved translatome remodeling in nematode species executing a shared developmental transition.

Michael Stadler,Gregory P. Copenhaver,Andrew Fire

doi:10.1371/journal.pgen.1003739

Abstract

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.

Highlights

Animals of diverse genera react to unfavorable growth conditions by entering developmentally arrested states known as diapause [1,2]
A salient feature of the observed regulation was the storage of idle mRNAs encoding key members of the protein synthesis machinery during metabolic arrest
The transition from L1 diapause to development. mRNA-seq measurements indicated that diapause exit triggered substantial remodeling of transcriptome composition in the four species, similar to the response previously described in C. elegans [7], with thousands of differentially expressed transcripts and expression changes spanning three orders of magnitude (Fig. 2A, Fig. S1)

Summary

Introduction

Animals of diverse genera react to unfavorable growth conditions by entering developmentally arrested states known as diapause [1,2]. C. elegans L1 diapause responses have been well characterized at the level of mRNA biogenesis, with developmental state changes associated with substantial transcriptional changes, the accumulation of RNA polymerase at gene promoters, and alternative splicing [7,8]. We selected four nematode species for investigation of the translation and mRNAlevel gene regulatory program associated with L1 diapause exit: two hermaphroditic species, Caenorhabditis elegans and C. briggsae, and two gonochoristic (male/female) species, C. remanei and C. brenneri (Fig. 1A). These four species exhibit highly similar morphologies and developmental timing despite significant genomic sequence divergence [9]. As a starting point for our analysis, we sought to examine the general character of the gene expression changes associated with

Author Summary

Findings

Materials and Methods