The lin-4 Regulatory RNA Controls Developmental Timing in Caenorhabditis elegans by Blocking LIN-14 Protein Synthesis after the Initiation of Translation
Abstract
lin-4 encodes a small RNA that is complementary to sequences in the 3' untranslated region (UTR) of lin-14 mRNA and that acts to developmentally repress the accumulation of LIN-14 protein. This repression is essential for the proper timing of numerous events of Caenorhabditis elegans larval development. We have investigated the mechanism of lin-4 RNA action by examining the fate of lin-14 mRNA in vivo during the time that lin-4 RNA is expressed. Our results indicate that the rate of synthesis of lin-14 mRNA, its state of polyadenylation, its abundance in the cytoplasmic fraction, and its polysomal sedimentation profile do not change in response to the accumulation of lin-4 RNA. Our results indicate that association of lin-4 RNA with the 3' UTR of lin-14 mRNA permits normal biogenesis of lin-14 mRNA, and normal translational initiation, but inhibits step(s) thereafter, such as translational elongation and/or the release of stable LIN-14 protein.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
lin-4 RNA binds to the 3' UTR of target mRNAs, including lin-28, and inhibits their translation.
“lin-4 RNA binds to the 3' UTR of target mRNAs, including lin-28, and inhibits their translation [27,45].”
From Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation (2004) · cites this paper as [27]
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 Olsen and Ambros 1999
Cites
The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14
Lee, R. C., Feinbaum, R. L., & Ambros, V. (1993) · Cell · doi:10.1016/0092-8674(93)90529-y · Cited by 12,948 · see citing works
Self-citationWightman, B., Ha, I., & Ruvkun, G. (1993) · Cell · doi:10.1016/0092-8674(93)90530-4 · Cited by 4,292 · see citing works
Iron regulates ferritin mRNA translation through a segment of its 5′-untranslated region.
Aziz, N., & Munro, H. N. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.23.8478 · Cited by 368 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mammalian microRNAs predominantly act to decrease target mRNA levels
Guo, H., Ingolia, N. T., Weissman, J. S., & Bartel, D. P. (2010) · Nature · doi:10.1038/nature09267 · Cited by 3,886 · see citing works
Regulation of mRNA Translation and Stability by microRNAs
Fabian, M. R., Sonenberg, N., & Filipowicz, W. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060308-103103 · Cited by 3,214 · see citing works
Processing of primary microRNAs by the Microprocessor complex
Denli, A. M., Tops, B. B. J., Plasterk, R. H. A., Ketting, R. F., & Hannon, G. J. (2004) · Nature · doi:10.1038/nature03049 · Cited by 2,784 · see citing works
Gene silencing by microRNAs: contributions of translational repression and mRNA decay
Huntzinger, E., & Izaurralde, E. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2936 · Cited by 2,339 · see citing works
FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism
Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y. S., Mele, A., Fraser, C. E., Stone, E. F., Chen, C., Fak, J. J., Chi, S. W., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.013 · Cited by 2,072 · see citing works
Sempere, L. F., Freemantle, S., Pitha-Rowe, I., Moss, E., Dmitrovsky, E., & Ambros, V. (2004) · Genome Biology · doi:10.1186/gb-2004-5-3-r13 · Cited by 1,578 · see citing works
Self-citationA microRNA array reveals extensive regulation of microRNAs during brain development
KRICHEVSKY, A. M., KING, K. S., DONAHUE, C. P., KHRAPKO, K., & KOSIK, K. S. (2003) · RNA · doi:10.1261/rna.5980303 · Cited by 1,040 · see citing works
Ribosome Profiling Shows That miR-430 Reduces Translation Before Causing mRNA Decay in Zebrafish
Bazzini, A. A., Lee, M. T., & Giraldez, A. J. (2012) · Science · doi:10.1126/science.1215704 · Cited by 709 · see citing works
PDL1 Regulation by p53 via miR-34
Cortez, M. A., Ivan, C., Valdecanas, D., Wang, X., Peltier, H. J., Ye, Y., Araujo, L., Carbone, D. P., Shilo, K., Giri, D. K., et al. (2016) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djv303 · Cited by 683 · see citing works
The power of the 3′ UTR: translational control and development.
Kuersten, S., & Goodwin, E. B. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1125 · Cited by 530 · see citing works
Most Caenorhabditis elegans microRNAs Are Individually Not Essential for Development or Viability
Miska, E. A., Alvarez-Saavedra, E., Abbott, A. L., Lau, N. C., Hellman, A. B., McGonagle, S. M., Bartel, D. P., Ambros, V. R., & Horvitz, H. R. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030215 · Cited by 484 · see citing works
“]. Binding of the silencing complex causes translational repression [”
BackgroundSelf-citationConcordant Regulation of Translation and mRNA Abundance for Hundreds of Targets of a Human microRNA
Hendrickson, D. G., Hogan, D. J., McCullough, H. L., Myers, J. W., Herschlag, D., Ferrell, J. E., & Brown, P. O. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000238 · Cited by 418 · see citing works
MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development
Boutz, P. L., Chawla, G., Stoilov, P., & Black, D. L. (2007) · Genes & Development · doi:10.1101/gad.1500707 · Cited by 304 · see citing works
Fragile X mental retardation protein is associated with translating polyribosomes in neuronal cells
Stefani, G., Fraser, C. E., Darnell, J. C., & Darnell, R. B. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.2306-04.2004 · Cited by 274 · see citing works
p16INK4a Translation Suppressed by miR-24
Lal, A., Kim, H. H., Abdelmohsen, K., Kuwano, Y., Pullmann, R., Srikantan, S., Subrahmanyam, R., Martindale, J. L., Yang, X., Ahmed, F., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001864 · Cited by 268 · see citing works
“elegans miRNA lin-4, which silenced lin-14 and lin-28 mRNAs without changing their polysomal distribution [34,35].”
microRNA strand selection: Unwinding the rules
Medley, J. C., Panzade, G., & Zinovyeva, A. Y. (2021) · WIREs RNA · doi:10.1002/wrna.1627 · Cited by 225 · see citing works
Small Interfering RNA-Mediated Gene Silencing in T Lymphocytes
McManus, M. T., Haines, B. B., Dillon, C. P., Whitehurst, C. E., van Parijs, L., Chen, J., & Sharp, P. A. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.10.5754 · Cited by 215 · see citing works
Braun, J. E., Huntzinger, E., & Izaurralde, E. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012328 · Cited by 61 · see citing works
Tian, W.-H., Wang, Z., Yue, Y.-X., Li, H., Li, Z.-J., Han, R.-L., Tian, Y.-D., Kang, X.-T., & Liu, X.-J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184420 · Cited by 35 · see citing works
Molotski, N., & Soen, Y. (2012) · RNA · doi:10.1261/rna.033142.112 · Cited by 26 · see citing works
- Authors
- Olsen, P. H., & Ambros, V.
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 1999-12
- Volume
- 216
- Issue
- 2
- Pages
- 671-680
- ISSN
- 0012-1606
- Cited by
- 969
- References
- 3
- Language
- en
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review