Nahar, Smita; Morales Moya, Lucas J; Brunner, Jana; Hendriks, Gert-Jan; Towbin, Benjamin; Hauser, Yannick P; Brancati, Giovanna; Gaidatzis, Dimos; Großhans, Helge (2024). Dynamics of miRNA accumulation during C. elegans larval development. (In Press). Nucleic acids research Oxford University Press 10.1093/nar/gkae115
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
08 Faculty of Science > Department of Biology > Institute of Cell Biology |
UniBE Contributor: |
Towbin, Benjamin Daniel |
Subjects: |
500 Science > 570 Life sciences; biology |
ISSN: |
0305-1048 |
Publisher: |
Oxford University Press |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
22 Feb 2024 11:15 |
Last Modified: |
23 Feb 2024 05:59 |
Publisher DOI: |
10.1093/nar/gkae115 |
PubMed ID: |
38381904 |
BORIS DOI: |
10.48350/193148 |
URI: |
https://boris.unibe.ch/id/eprint/193148 |
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