TY - JOUR
T1 - 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
AU - Forbes-Beadle, Lauren
AU - Love, Jennifer
AU - Shapovalova, Yuliya
AU - Artemev, Artem
AU - Rattray, Magnus
AU - Ashe, Hilary
PY - 2023/1/17
Y1 - 2023/1/17
N2 - 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.
AB - 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.
KW - Drosophila/genetics
KW - RNA Stability/genetics
KW - Animals
KW - Single Molecule Imaging
KW - Processing Bodies
KW - RNA, Messenger/genetics
UR - https://www.scopus.com/pages/publications/85146923298
U2 - 10.1371/journal.pbio.3001956
DO - 10.1371/journal.pbio.3001956
M3 - Article
C2 - 36649329
SN - 1545-7885
VL - 21
JO - PLoS Biology
JF - PLoS Biology
IS - 1
M1 - e3001956
ER -