Dynamics of miRNA accumulation during C. elegans larval development.

Autor:	Nahar S; Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland., Morales Moya LJ; Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland., Brunner J; Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.; University of Basel, Basel, Switzerland., Hendriks GJ; Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland., Towbin B; Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.; University of Bern, Bern, Switzerland., Hauser YP; Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.; University of Basel, Basel, Switzerland., Brancati G; Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.; University of Basel, Basel, Switzerland., Gaidatzis D; Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.; SIB Swiss Institute of Bioinformatics, Basel, Switzerland., Großhans H; Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.; University of Basel, Basel, Switzerland.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 May 22; Vol. 52 (9), pp. 5336-5355.
DOI:	10.1093/nar/gkae115
Abstrakt:	Temporally and spatially controlled accumulation underlies the functions of microRNAs (miRNAs) in various developmental processes. In Caenorhabditis elegans, this is exemplified by the temporal patterning miRNAs lin-4 and let-7, but for most miRNAs, developmental expression patterns remain poorly resolved. Indeed, experimentally observed long half-lives may constrain possible dynamics. Here, we profile miRNA expression throughout C. elegans postembryonic development at high temporal resolution, which identifies dynamically expressed miRNAs. We use mathematical models to explore the underlying mechanisms. For let-7, we can explain, and experimentally confirm, a striking stepwise accumulation pattern through a combination of rhythmic transcription and stage-specific regulation of precursor processing by the RNA-binding protein LIN-28. By contrast, the dynamics of several other miRNAs cannot be explained by regulation of production rates alone. Specifically, we show that a combination of oscillatory transcription and rhythmic decay drive rhythmic accumulation of miR-235, orthologous to miR-92 in other animals. We demonstrate that decay of miR-235 and additional miRNAs depends on EBAX-1, previously implicated in target-directed miRNA degradation (TDMD). Taken together, our results provide insight into dynamic miRNA decay and establish a resource to studying both the developmental functions of, and the regulatory mechanisms acting on, miRNAs. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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