ArticleProceedings of the National Academy of Sciences of the United States of America2014
Caenorhabditis elegans period homolog lin-42 regulates the timing of heterochronic miRNA expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Meta-analysis of Caenorhabditis elegans single-cell developmental data reveals multi-frequency oscillation in gene activation.Bioinformatics (Oxford, England) · 2020Pooled it
- FOXO/DAF-16 modulates the transcription factor ROR/NHR-23 and inhibits thebioRxiv : the preprint server for biology · 2026Article
- A molecular timer couples organism-wide temporal identity to developmental checkpoints.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A developmental timer coordinates organism-wide microRNA transcription.bioRxiv : the preprint server for biology · 2026Article
- Circadian-shaped immune variability predicts infection outcome.Science advances · 2026Article
- A conserved chronobiological complex times C. elegans development.The EMBO journal · 2025Article
- Systematic identification of oscillatory gene expression in single cell types.bioRxiv : the preprint server for biology · 2025Article
- FLYWCH transcription factors act in a LIN-42/Period autoregulatory loop during gonad migration inbioRxiv : the preprint server for biology · 2025Article
- A wrinkle in timers: evolutionary rewiring of conserved biological timekeepers.Trends in biochemical sciences · 2025Review
- Essential function of transmembrane transcription factor MYRF in promoting transcription of miRNAeLife · 2024Article
- Clock gene homologs lin-42 and kin-20 regulate circadian rhythms in C. elegans.Scientific reports · 2024Article
- A lineage-resolved cartography of microRNA promoter activity in C. elegans empowers multidimensional developmental analysis.Nature communications · 2024Article
- Recent advances in understanding microRNA function and regulation in C. elegans.Seminars in cell & developmental biology · 2024Review
- A circadian-like gene network programs the timing and dosage of heterochronic miRNA transcription during C. elegans development.Developmental cell · 2023Article
- A spatiotemporal reconstruction of theeLife · 2022Article
- Article
- Let-7 as a Promising Target in Aging and Aging-Related Diseases: A Promise or a Pledge.Biomolecules · 2022Review
- Temporal scaling inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- daf-16/FOXO blocks adult cell fate in Caenorhabditis elegans dauer larvae via lin-41/TRIM71.PLoS genetics · 2021Article
- Review
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2 authors at 1 institution in 1 country.
Funding
Abstract
MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally via the 3' UTR of target mRNAs and were first identified in the Caenorhabditis elegans heterochronic pathway. miRNAs have since been found in many organisms and have broad functions, including control of differentiation and pluripotency in humans. lin-4 and let-7-family miRNAs regulate developmental timing in C. elegans, and their proper temporal expression ensures cell lineage patterns are correctly timed and sequentially executed. Although much is known about miRNA biogenesis, less is understood about how miRNA expression is timed and regulated. lin-42, the worm homolog of the circadian rhythm gene period of flies and mammals, is another core component of the heterochronic gene pathway. lin-42 mutants have a precocious phenotype, in which later-stage programs are executed too early, but the placement of lin-42 in the timing pathway is unclear. Here, we demonstrate that lin-42 negatively regulates heterochronic miRNA transcription. let-7 and the related miRNA miR-48 accumulate precociously in lin-42 mutants. This defect reflects transcriptional misregulation because enhanced expression of both primary miRNA transcripts (pri-miRNAs) and a let-7 promoter::gfp fusion are observed. The pri-miRNA levels oscillate during larval development, in a pattern reminiscent of lin-42 expression. Importantly, we show that lin-42 is not required for this cycling; instead, peak amplitude is increased. Genetic analyses further confirm that lin-42 acts through let-7 family miRNAs. Taken together, these data show that a key function of lin-42 in developmental timing is to dampen pri-miRNAs levels, preventing their premature expression as mature miRNAs.
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