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Norway

PMID:38381904  

Dynamics of miRNA accumulation during C. elegans larval development.

Smita Nahar | Lucas J Morales Moya | Jana Brunner | Gert-Jan Hendriks | Benjamin Towbin | Yannick P Hauser | Giovanna Brancati | Dimos Gaidatzis | Helge Großhans
Nucleic acids research | 2024

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.

Pubmed ID: 38381904

Associated grants

  • Agency: H2020 European Research Council,
    Id: 741269
  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: Boehringer Ingelheim Fonds,
  • Agency: Novartis Stiftung für Medizinisch-Biologische Forschung,
  • Agency: FP7 Ideas,
  • Agency: European Research Council, International
    Id: 241985
  • Agency: H2020 Marie Skłodowska-Curie Actions,
    Id: 842386
  • Agency: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung,
    Id: 310030_188487

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