Transient ribosome slowdown at the decoding step triggers mRNA degradation independent of Znf598 in zebrafish

Abstract

The control of mRNA stability plays a central role in regulating gene expression patterns. Recent studies have revealed that codon composition in the open reading frame (ORF) determines mRNA stability in multiple organisms. Based on genome-wide correlation approaches, this previously unrecognized role of the genetic code is attributable to the kinetics of the codon-decoding process by the ribosome. However, complementary experimental analysis is required to define the codon effects on mRNA stability apart from the related cotranslational mRNA decay pathways such as those triggered by aberrant ribosome stalls. In the current study, we performed a set of reporter-based analyses to define codon-mediated mRNA decay and ribosome stall-dependent mRNA decay in zebrafish embryos. Our analysis showed that the effect of codons on mRNA stability stems from the decoding process, independent of Znf598 and stall-dependent mRNA decay. We propose that codon-mediated mRNA decay is triggered by transiently slowed ribosomes engaging in a productive translation cycle in zebrafish embryos.