Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans

Wightman, Bruce; Ha, Ilho; Ruvkun, Gary

doi:10.1016/0092-8674(93)90530-4

Cited by 4,292Developmental Biology and Gene RegulationRNA Research and SplicingRNA and protein synthesis mechanisms

Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans

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Wightman, Bruce, Ha, Ilho, Ruvkun, Gary·1993·Cell

DOI 10.1016/0092-8674(93)90530-4

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Abstract

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]
Two C. elegans miRNAs, lin-4 and let-7, control developmental timing by forming imperfect base pairing with elements within the 3' UTR of target mRNAs and attenuating their translation.
“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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Authors: Wightman, B., Ha, I., & Ruvkun, G.
Affiliations: Massachusetts General Hospital (US)
ORCID: Wightman, Bruce
Ruvkun, Gary
Venue: Cell
Publisher: Elsevier BV
Published: 1993-12
Volume: 75
Issue: 5
Pages: 855-862
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/0092-8674(93)90530-4
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans

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