The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14
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lin-4 is essential for the normal temporal control of diverse postembryonic developmental events in C. elegans. lin-4 acts by negatively regulating the level of LIN-14 protein, creating a temporal decrease in LIN-14 protein starting in the first larval stage (L1). We have cloned the C. elegans lin-4 locus by chromosomal walking and transformation rescue. We used the C. elegans clone to isolate the gene from three other Caenorhabditis species; all four Caenorhabditis clones functionally rescue the lin-4 null allele of C. elegans. Comparison of the lin-4 genomic sequence from these four species and site-directed mutagenesis of potential open reading frames indicated that lin-4 does not encode a protein. Two small lin-4 transcripts of approximately 22 and 61 nt were identified in C. elegans and found to contain sequences complementary to a repeated sequence element in the 3' untranslated region (UTR) of lin-14 mRNA, suggesting that lin-4 regulates lin-14 translation via an antisense RNA-RNA interaction.
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MicroRNAs are short non-coding RNAs that regulate gene expression and act as important regulators of cellular phenotype and function.
“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 [1]
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 Lee et al. 1993
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- Authors
- Lee, R. C., Feinbaum, R. L., & Ambros, V.
- Affiliations
- Harvard University (US)
- ORCID
- Ambros, Victor
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1993-12
- Volume
- 75
- Issue
- 5
- Pages
- 843-854
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2138664009
- Cited by
- 12,948
- References
- 54
- Citations by year
- 2026: 243 · 2025: 483 · 2024: 498 · 2023: 525 · 2022: 682 · 2021: 688 · 2020: 702 · 2019: 683 · 2018: 671 · 2017: 713 · 2016: 684 · 2015: 780 · 2014: 827 · 2013: 862 · 2012: 760
- FWCI
- 8.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Massachusetts General Hospital
- National Institutes of Health
- National Institute of General Medical Sciences (GM34028, R01GM034028, GM15396)
- 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 › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- lin-4, lin-14, heterochrony, small RNA, antisense RNA, RNA-RNA interactions, protein synthesis inhibition, 3' untranslated region, postembryonic development, Caenorhabditis, gene cloning, temporal gene regulation
- MeSH terms
- Animals, Base Sequence, Caenorhabditis, Gene Expression Regulation, Hydrogen Bonding, Molecular Sequence Data, Nucleic Acid Conformation, Phylogeny, RNA, Messenger, Sequence Homology, Nucleic Acid, Time Factors, Protein Biosynthesis, Helminth Proteins, RNA, Antisense, Sequence Alignment, Genes, Helminth, DNA Primers
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