The lin-41 RBCC Gene Acts in the C. elegans Heterochronic Pathway between the let-7 Regulatory RNA and the LIN-29 Transcription Factor
Open accessAbstract
Null mutations in the C. elegans heterochronic gene lin-41 cause precocious expression of adult fates at larval stages. Increased lin-41 activity causes the opposite phenotype, reiteration of larval fates. let-7 mutations cause similar reiterated heterochronic phenotypes that are suppressed by lin-41 mutations, showing that lin-41 is negatively regulated by let-7. lin-41 negatively regulates the timing of LIN-29 adult specification transcription factor expression. lin-41 encodes an RBCC protein, and two elements in the lin-413'UTR are complementary to the 21 nucleotide let-7 regulatory RNA. A lin-41::GFP fusion gene is downregulated in the tissues affected by lin-41 at the time that the let-7 regulatory RNA is upregulated. We suggest that late larval activation of let-7 RNA expression downregulates LIN-41 to relieve inhibition of lin-29.
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NHL domains have been shown to be important for the function of a number of proteins, including LIN41 in Caenorhabditis elegans and brat in Drosophila melanogaster, both of which act as posttranscriptional repressors.
“NHL domains have been shown to be important for the function of a number of proteins-including LIN41, in Caenorhabditis elegans, and brat, in Drosophila melanogaster, both of which act as posttranscriptional repressors.”
From Limb-Girdle Muscular Dystrophy Type 2H Associated with Mutation in TRIM32, a Putative E3-Ubiquitin–Ligase Gene (2002) · cites this paper as Slack et al. 2000
All of these mutations abolish an interaction with another protein, thereby leading to functional consequences.
“All of these mutations abolish an interaction with another protein, thereby leading to functional consequences.”
From Limb-Girdle Muscular Dystrophy Type 2H Associated with Mutation in TRIM32, a Putative E3-Ubiquitin–Ligase Gene (2002) · cites this paper as Slack et al. 2000
Of the seven apparent loss-of-function lin41 mutations discussed by Slack et al. (2000), five lead to amino acid substitutions found in the NHL domains.
“Of the seven apparent loss-of-function lin41 mutations that are discussed by Slack et al. (2000), five lead to amino acid substitutions found in the NHL domains”
From Limb-Girdle Muscular Dystrophy Type 2H Associated with Mutation in TRIM32, a Putative E3-Ubiquitin–Ligase Gene (2002) · cites this paper as Slack et al. 2000
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- Authors
- Slack, F. J., Basson, M., Liu, Z., Ambros, V., Horvitz, H. R., & Ruvkun, G.
- Affiliations
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Dartmouth College (US)
- Corresponding author
- Ruvkun, Gary
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2000-04
- Volume
- 5
- Issue
- 4
- Pages
- 659-669
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2123580197
- Cited by
- 751
- References
- 42
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 20 · 2023: 23 · 2022: 18 · 2021: 26 · 2020: 21 · 2019: 32 · 2018: 24 · 2017: 27 · 2016: 21 · 2015: 30 · 2014: 24 · 2013: 36 · 2012: 26
- FWCI
- 11.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- U.S. Public Health Service (GM34028)
- Israel National Road Safety Authority (GM18663, GM24663)
- National Institutes of Health (GM44619)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- lin-41, heterochrony, let-7 microRNA, Caenorhabditis elegans, developmental timing, 3' untranslated region, microRNA target regulation, larval development
- MeSH terms
- Alleles, Amino Acid Sequence, Animals, Base Sequence, DNA-Binding Proteins, Multigene Family, Molecular Sequence Data, Mutation, Time Factors, Tissue Distribution, Transcription Factors, Down-Regulation, Helminth Proteins, Zinc Fingers, Caenorhabditis elegans, Genes, Helminth, Gene Expression Regulation, Developmental, RNA, Helminth, Body Patterning, 3' Untranslated Regions, Caenorhabditis elegans Proteins
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