ArticlePLoS genetics2012
lin-28 controls the succession of cell fate choices via two distinct activities.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 85 citations in OpenAlex.
- let-7 miRNA and lin-46 mRNA are essential targets of the LIN28 RNA-binding protein in Caenorhabditis elegans developmental timing regulation.PLoS biology · 2026Article
- Multi-dimensional regulation of LIN-28 temporal expression dynamics in the C. elegans heterochronic gene cascade.Development (Cambridge, England) · 2026Article
- LIN28-mediated gene regulatory loops synchronize transitions throughout organogenesis.Biochemistry and biophysics reports · 2025Article
- Somatic gonad morphogenesis in C. elegans requires the heterochronic pathway acting through HBL-1.G3 (Bethesda, Md.) · 2025Article
- Poised PABP-RNA hubs implement signal-dependent mRNA decay in development.Nature structural & molecular biology · 2024Article
- A temporal sequence of heterochronic gene activities promotes stage-specific developmental events in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2024Article
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- Orthologs of the Caenorhabditis elegans heterochronic genes have divergent functions in Caenorhabditis briggsae.Genetics · 2023Article
- A DEAD-box helicase drives the partitioning of a pro-differentiation NAB protein into nuclear foci.Nature communications · 2023Article
- Two intrinsic timing mechanisms set start and end times for dendritic arborization of a nociceptive neuron.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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- C. elegans LIN-28 controls temporal cell fate progression by regulating LIN-46 expression via the 5' UTR of lin-46 mRNA.Cell reports · 2021Article
- Lin28 paralogs regulate lung branching morphogenesis.Cell reports · 2021Article
- The multifaceted roles of microRNAs in differentiation.Current opinion in cell biology · 2020Review
- Upregulating Lin28a Promotes Axon Regeneration in Adult Mice with Optic Nerve and Spinal Cord Injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Lin28 reprograms inner ear glia to a neuronal fate.Stem cells (Dayton, Ohio) · 2020Article
- A branched heterochronic pathway directs juvenile-to-adult transition through two LIN-29 isoforms.eLife · 2020Article
- Regulation of nuclear-cytoplasmic partitioning by theDevelopment (Cambridge, England) · 2019Article
- The MakorineLife · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
lin-28 is a conserved regulator of cell fate succession in animals. In Caenorhabditis elegans, it is a component of the heterochronic gene pathway that governs larval developmental timing, while its vertebrate homologs promote pluripotency and control differentiation in diverse tissues. The RNA binding protein encoded by lin-28 can directly inhibit let-7 microRNA processing by a novel mechanism that is conserved from worms to humans. We found that C. elegans LIN-28 protein can interact with four distinct let-7 family pre-microRNAs, but in vivo inhibits the premature accumulation of only let-7. Surprisingly, however, lin-28 does not require let-7 or its relatives for its characteristic promotion of second larval stage cell fates. In other words, we find that the premature accumulation of mature let-7 does not account for lin-28's precocious phenotype. To explain let-7's role in lin-28 activity, we provide evidence that lin-28 acts in two steps: first, the let-7-independent positive regulation of hbl-1 through its 3'UTR to control L2 stage-specific cell fates; and second, a let-7-dependent step that controls subsequent fates via repression of lin-41. Our evidence also indicates that let-7 functions one stage earlier in C. elegans development than previously thought. Importantly, lin-28's two-step mechanism resembles that of the heterochronic gene lin-14, and the overlap of their activities suggests a clockwork mechanism for developmental timing. Furthermore, this model explains the previous observation that mammalian Lin28 has two genetically separable activities. Thus, lin-28's two-step mechanism may be an essential feature of its evolutionarily conserved role in cell fate succession.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.