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Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans
Open accessAbstract
During C. elegans development, the temporal pattern of many cell lineages is specified by graded activity of the heterochronic gene Lin-14. Here we demonstrate that a temporal gradient in Lin-14 protein is generated posttranscriptionally by multiple elements in the lin-14 3'UTR that are regulated by the heterochronic gene Lin-4. The lin-14 3'UTR is both necessary and sufficient to confer lin-4-mediated posttranscriptional temporal regulation. The function of the lin-14 3'UTR is conserved between C. elegans and C. briggsae. Among the conserved sequences are seven elements that are each complementary to the lin-4 RNAs. A reporter gene bearing three of these elements shows partial temporal gradient activity. These data suggest a molecular mechanism for Lin-14p temporal gradient formation: the lin-4 RNAs base pair to sites in the lin-14 3'UTR to form multiple RNA duplexes that down-regulate lin-14 translation.
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“MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and thus act as important regulators of cellular phenotype and function.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [2]
In the citing paper
“Two C. elegans miRNAs, lin-4 and let-7, control developmental timing by forming imperfect base pairing with elements within the 3Ј UTR of target mRNAs and attenuating their translation (Lee et al. 1993;Wightman et al. 1993;Olsen and Ambros 1999;Reinhart et al. 2000;Slack et al. 2000).”
From A microRNA array reveals extensive regulation of microRNAs during brain development (2003) · cites this paper as Wightman et al. 1993
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Metadata
- Authors
- Wightman, B., Ha, I., & Ruvkun, G.
- Affiliations
- Massachusetts General Hospital (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1993-12
- Volume
- 75
- Issue
- 5
- Pages
- 855-862
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2160467221
- Cited by
- 4,292
- References
- 27
- Citations by year
- 2026: 86 · 2025: 189 · 2024: 151 · 2023: 164 · 2022: 171 · 2021: 193 · 2020: 177 · 2019: 172 · 2018: 189 · 2017: 235 · 2016: 193 · 2015: 227 · 2014: 224 · 2013: 281 · 2012: 231
- FWCI
- 6.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM44619, R01GM044619)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- lin-14, lin-4, post-transcriptional regulation, 3' untranslated region, heterochronic genes, RNA duplex, protein synthesis inhibition, Caenorhabditis elegans, Caenorhabditis briggsae, developmental timing, cell lineage specification
- MeSH terms
- Animals, Base Sequence, Caenorhabditis, Gene Expression Regulation, Molecular Sequence Data, Morphogenesis, RNA, Messenger, Sequence Homology, Nucleic Acid, Species Specificity, Time Factors, Protein Biosynthesis, Helminth Proteins, RNA, Antisense, Sequence Alignment, Genes, Helminth
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