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

PLoS Biol. 2023 Jan 17;21(1):e3001956. doi: 10.1371/journal.pbio.3001956. eCollection 2023 Jan.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • RNA, Messenger