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

Lauren Forbes-Beadle, Jennifer Love, Yuliya Shapovalova, Artem Artemev, Magnus Rattray, Hilary Ashe

Research output: Contribution to journalArticlepeer-review

Abstract

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 30 ends in P-bodies in the early embryo, consistent with 50 to 30 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.

Original languageEnglish
Article numbere3001956
JournalPLoS Biology
Volume21
Issue number1
DOIs
Publication statusPublished - 17 Jan 2023

Keywords

  • Drosophila/genetics
  • RNA Stability/genetics
  • Animals
  • Single Molecule Imaging
  • Processing Bodies
  • RNA, Messenger/genetics

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