Combined modelling of mRNA decay dynamics and single-molecule imaging in the Drosophila embryo uncovers a role for P-bodies in 5' to 3' degradation

• Published in: PLoS biology Vol. 21; no. 1; p. e3001956
• Main Authors: Forbes Beadle, Lauren, Love, Jennifer C, Shapovalova, Yuliya, Artemev, Artem, Rattray, Magnus, Ashe, Hilary L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17-01-2023; Public Library of Science (PLoS)
• Subjects: Animals; Biodegradation; Biology and life sciences; Cell fate; Degradation; Drosophila; Drosophila - genetics; Drosophila - metabolism; Dynamic stability; Embryo; Embryogenesis; Embryonic growth stage; Embryos; Fruit flies; Gaussian process; Gene expression; Genetic aspects; Genomes; Half-life; Insects; Labeling; Labelling; Messenger RNA; mRNA stability; mRNA turnover; Physiological aspects; Processing Bodies; Regression models; Research and Analysis Methods; RNA Stability - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Single Molecule Imaging; Time series; United Kingdom
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3001956

Regulation of mRNA degradation is critical for a diverse array of cellular processes and developmental cell fate decisions. Many methods for determining mRNA half-lives rely on transcriptional inhibition or metabolic labelling. Here, we use a non-invasive method for estimating half-lives for hundreds of mRNAs in the early Drosophila embryo. This approach uses the intronic and exonic reads from a total RNA-seq time series and Gaussian process regression to model the dynamics of premature and mature mRNAs. We show how regulation of mRNA stability is used to establish a range of mature mRNA dynamics during embryogenesis, despite shared transcription profiles. Using single-molecule imaging, we provide evidence that, for the mRNAs tested, there is a correlation between short half-life and mRNA association with P-bodies. Moreover, we detect an enrichment of mRNA 3' ends in P-bodies in the early embryo, consistent with 5' to 3' degradation occurring in P-bodies for at least a subset of mRNAs. We discuss our findings in relation to recently published data suggesting that the primary function of P-bodies in other biological contexts is mRNA storage.