Translation-dependent remodeling of the mRNA structure landscape in early-stage vertebrate embryos (#6)
RNA folding plays a pivotal role in RNA function. However, our current knowledge on RNA structure is largely limited to structural predictions and in vitro measurements, where interactions with cellular factors are ignored, limiting our understanding of RNA structure-function in vivo. Here we applied DMS-seq to analyze the global map of RNA structures in zebrafish embryos, comparing the mRNA structure landscape in vivo, in vitro and under the presence of translation inhibitors. We find that cellular factors, not only limited to the ribosome, remodel RNA structures in a translation-dependent manner. Indeed, highly translated CDS and uORF present increased accessibility (lower structure) in vivo, in agreement with the unwinding activity of the ribosome. In contrast, poorly translated mRNAs globally adopt higher-order structures in their 3'UTR regions in vivo than in vitro, and therefore are likely involved in translation repression. These differences, as well as the observed trinucleotide periodicity, are lost in in vitro folded transcripts, or when translation initiation is inhibited, supporting the central role of ribosomes as major determinants shaping the in vivo RNA structure landscape.