Gene Symbol: F59G1.6
Description: miscRNA
Species: Caenorhabditis elegans
Products:     F59G1.6

Top Publications

  1. Lin S, Johnson S, Abraham M, Vella M, Pasquinelli A, Gamberi C, et al. The C elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target. Dev Cell. 2003;4:639-50 pubmed
    ..MicroRNAs may likewise function to regulate Drosophila hunchback during temporal patterning of the nervous system. ..
  2. Sempere L, Sokol N, Dubrovsky E, Berger E, Ambros V. Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and broad-Complex gene activity. Dev Biol. 2003;259:9-18 pubmed
  3. Moss E, Lee R, Ambros V. The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell. 1997;88:637-46 pubmed
    ..Deleting the LCE produces a dominant gain-of-function allele that causes a retarded phenotype, indicating that lin-28 activity is a switch that controls choices of stage-specific fates. ..
  4. Boehm M, Slack F. A developmental timing microRNA and its target regulate life span in C. elegans. Science. 2005;310:1954-7 pubmed
    ..This work reveals a role for microRNAs and developmental timing genes in life-span regulation. ..
  5. Olsen P, Ambros V. The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol. 1999;216:671-80 pubmed
  6. Ha I, Wightman B, Ruvkun G. A bulged lin-4/lin-14 RNA duplex is sufficient for Caenorhabditis elegans lin-14 temporal gradient formation. Genes Dev. 1996;10:3041-50 pubmed
    ..This suggests that a specific secondary structure of lin-4/lin-14 RNA duplex that may be recognized by an accessory protein, rather than an RNA duplex per se, is required in vivo for the generation of the LIN-14 temporal gradient. ..
  7. Ding X, Grosshans H. Repression of C. elegans microRNA targets at the initiation level of translation requires GW182 proteins. EMBO J. 2009;28:213-22 pubmed publisher
    ..elegans as a genetic system for dissection of the underlying mechanisms. ..
  8. Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993;75:855-62 pubmed
    ..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. ..
  9. Lee R, Feinbaum R, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843-54 pubmed
    ..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...

More Information


  1. Ambros V. A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans. Cell. 1989;57:49-57 pubmed
    ..lin-29 may activate the L/A switch by regulating genes that control cell division, differentiation, and stage-specific gene expression in hypodermal cells. ..
  2. Feinbaum R, Ambros V. The timing of lin-4 RNA accumulation controls the timing of postembryonic developmental events in Caenorhabditis elegans. Dev Biol. 1999;210:87-95 pubmed
    ..These results indicate that the temporal profile of lin-4 RNA accumulation specifies the timing of LIN-14 down-regulation and thereby controls the timing of postembryonic developmental events. ..
  3. Nashimoto M. Anomalous RNA substrates for mammalian tRNA 3' processing endoribonuclease. FEBS Lett. 2000;472:179-86 pubmed
    ..We also demonstrated that an RNA complex of lin-4 and lin-14 from Caenorhabditis elegans can be recognized and cleaved by pig 3' tRNase. ..
  4. Slack F, Ruvkun G. Temporal pattern formation by heterochronic genes. Annu Rev Genet. 1997;31:611-34 pubmed
    ..Hormonal control of developmental timing is a common theme throughout phylogeny. Heterochronic genes that involve hormonal signaling have been identified in vertebrates as well as C. elegans. ..
  5. Ruvkun G, Wightman B, Burglin T, Arasu P. Dominant gain-of-function mutations that lead to misregulation of the C. elegans heterochronic gene lin-14, and the evolutionary implications of dominant mutations in pattern-formation genes. Dev Suppl. 1991;1:47-54 pubmed
    ..The normal down-regulation of lin-14 within 10 h of hatching is not determined by the passage of time per se, but rather is triggered when feeding induces post-embryonic development.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  6. Lee R, Feinbaum R, Ambros V. A short history of a short RNA. Cell. 2004;116:S89-92, 1 p following S96 pubmed
  7. Chalfie M, Horvitz H, Sulston J. Mutations that lead to reiterations in the cell lineages of C. elegans. Cell. 1981;24:59-69 pubmed
    ..We suggest that the wild-type unc-86 and lin-4 genes act to modify latent reiterative cell lineages, which are revealed when the activity of one of these genes is eliminated. ..
  8. Euling S, Ambros V. Heterochronic genes control cell cycle progress and developmental competence of C. elegans vulva precursor cells. Cell. 1996;84:667-76 pubmed
    ..A genetic pathway that includes lin-4, lin-14, and lin-28 controls when VPCs complete G1 and also controls when VPCs acquire the competence to respond to the intercellular patterning signals and express vulval fates. ..
  9. Grishok A, Pasquinelli A, Conte D, Li N, Parrish S, Ha I, et al. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell. 2001;106:23-34 pubmed
    ..Our findings suggest that a common processing machinery generates guide RNAs that mediate both RNAi and endogenous gene regulation. ..
  10. Abrahante J, Miller E, Rougvie A. Identification of heterochronic mutants in Caenorhabditis elegans. Temporal misexpression of a collagen::green fluorescent protein fusion gene. Genetics. 1998;149:1335-51 pubmed
    ..Two mutations define a new gene, lin-58. When separated from lin-4, the lin-58 mutations cause precocious seam cell terminal differentiation and thus define a new member of the heterochronic gene pathway. ..
  11. Mitani S, Du H, Hall D, Driscoll M, Chalfie M. Combinatorial control of touch receptor neuron expression in Caenorhabditis elegans. Development. 1993;119:773-83 pubmed
  12. Ambros V. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell. 2003;113:673-6 pubmed
    ..In C. elegans, a homolog of the well-known fly developmental regulator hunchback acts downstream of the microRNAs lin-4 and let-7 in a pathway controlling developmental timing. ..
  13. Seggerson K, Tang L, Moss E. Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin-28 after translation initiation. Dev Biol. 2002;243:215-25 pubmed
    ..The role of lin-4 may be to initiate or potentiate the lin-4-independent circuit. We speculate that a parallel lin-4-independent regulatory mechanism regulates the expression of lin-14. ..
  14. Ambros V, Moss E. Heterochronic genes and the temporal control of C. elegans development. Trends Genet. 1994;10:123-7 pubmed
  15. Hong Y, Lee R, Ambros V. Structure and function analysis of LIN-14, a temporal regulator of postembryonic developmental events in Caenorhabditis elegans. Mol Cell Biol. 2000;20:2285-95 pubmed
    ..These results support the view that LIN-14 controls developmental timing in C. elegans by regulating gene expression in the nucleus. ..
  16. Horvitz H, Sternberg P, Greenwald I, Fixsen W, Ellis H. Mutations that affect neural cell lineages and cell fates during the development of the nematode Caenorhabditis elegans. Cold Spring Harb Symp Quant Biol. 1983;48 Pt 2:453-63 pubmed
    ..abstract truncated at 400 words) ..
  17. Liu F, Thatcher J, Epstein H. Induction of glyoxylate cycle expression in Caenorhabditis elegans: a fasting response throughout larval development. Biochemistry. 1997;36:255-60 pubmed
  18. Delihas N. Regulation of gene expression by trans-encoded antisense RNAs. Mol Microbiol. 1995;15:411-4 pubmed
    ..It is possible that currently known unlinked antisense RNA genes are part of a larger class of heretofore undiscovered regulatory RNA genes. Possible ways of detecting other unlinked antisense RNA genes are discussed. ..
  19. Zhu C, Ji C, Zhang C, Gao C, Zhu J, Qin D, et al. The lin-4 gene controls fat accumulation and longevity in Caenorhabditis elegans. Int J Mol Sci. 2010;11:4814-25 pubmed publisher
    ..Taken together, our findings suggest that lin-4 may play an important role in regulating fat accumulation and locomotion and that lin-4 may control the life span of C. elegans by mediating ROS production. ..
  20. Johnson S, Lin S, Slack F. The time of appearance of the C. elegans let-7 microRNA is transcriptionally controlled utilizing a temporal regulatory element in its promoter. Dev Biol. 2003;259:364-79 pubmed
    ..We speculate that these heterochronic genes regulate let-7 expression through its TRE. ..
  21. Reinhart B, Slack F, Basson M, Pasquinelli A, Bettinger J, Rougvie A, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000;403:901-6 pubmed
    ..We propose that the sequential stage-specific expression of the lin-4 and let-7 regulatory RNAs triggers transitions in the complement of heterochronic regulatory proteins to coordinate developmental timing. ..
  22. Austin J, Kenyon C. Developmental timekeeping. Marking time with antisense. Curr Biol. 1994;4:366-9 pubmed
    ..Post-transcriptional regulation of the heterochronic gene lin-14 by the binding of a natural antisense RNA controls the temporal pattern of larval development in the nematode Caenorhabditis elegans. ..
  23. Moss E, Tang L. Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites. Dev Biol. 2003;258:432-42 pubmed
    ..elegans lin-4 and let-7 microRNAs, suggesting that microRNA regulation is a conserved feature of the Lin-28 gene in diverse animals. ..
  24. Rougvie A, Ambros V. The heterochronic gene lin-29 encodes a zinc finger protein that controls a terminal differentiation event in Caenorhabditis elegans. Development. 1995;121:2491-500 pubmed
    ..lin-29 mRNA is detected in the first larval stage and increases in abundance through subsequent larval stages until the final molt, when lin-29 activity is required for terminal differentiation. ..
  25. Lee R, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science. 2001;294:862-4 pubmed
    ..elegans larval development, and three of them have apparent homologs in mammals and/or insects. Small noncoding RNAs of the miRNA class appear to be numerous and diverse. ..
  26. Bashirullah A, Pasquinelli A, Kiger A, Perrimon N, Ruvkun G, Thummel C. Coordinate regulation of small temporal RNAs at the onset of Drosophila metamorphosis. Dev Biol. 2003;259:1-8 pubmed
  27. Banerjee D, Slack F. Control of developmental timing by small temporal RNAs: a paradigm for RNA-mediated regulation of gene expression. Bioessays. 2002;24:119-29 pubmed
    ..We postulate that other small non-coding RNAs may function as stRNAs to control temporal identity during development in C. elegans and other organisms. ..
  28. Horvitz H, Sulston J. Isolation and genetic characterization of cell-lineage mutants of the nematode Caenorhabditis elegans. Genetics. 1980;96:435-54 pubmed
    ..Three of the mutants are suppressed by pleiotropic suppressors believed to be specific for null alleles, suggesting that their phenotypes result from the complete absence of gene activity. ..
  29. Shi Z, Hayes G, Ruvkun G. Dual regulation of the lin-14 target mRNA by the lin-4 miRNA. PLoS ONE. 2013;8:e75475 pubmed publisher
    ..Our results point to the importance of translational inhibition in silencing of lin-14 by the lin-4 miRNA. ..
  30. Wickens M, Takayama K. RNA. Deviants--or emissaries. Nature. 1994;367:17-8 pubmed
  31. Turner M, Jiao A, Slack F. Autoregulation of lin-4 microRNA transcription by RNA activation (RNAa) in C. elegans. Cell Cycle. 2014;13:772-81 pubmed publisher
    ..Thus, we describe the first in vivo evidence of RNA activation (RNAa) by an endogenous miRNA, and provide new insights into an elegant autoregulatory mechanism that ensures the proper timing of stem cell fate decisions in development. ..
  32. Zou Y, Chiu H, Domenger D, Chuang C, Chang C. The lin-4 microRNA targets the LIN-14 transcription factor to inhibit netrin-mediated axon attraction. Sci Signal. 2012;5:ra43 pubmed publisher
    ..LIN-14 stimulated UNC-6-mediated axon attraction in part by increasing UNC-40 abundance. Our study indicated that lin-4 microRNA reduced the activity of LIN-14 to terminate UNC-6-mediated axon guidance of AVM neurons. ..
  33. Xu Y, Quinn C. Transition between synaptic branch formation and synaptogenesis is regulated by the lin-4 microRNA. Dev Biol. 2016;420:60-66 pubmed publisher
    ..These observations provide a novel mechanism whereby lin-4 promotes the transition from branch formation to synaptogenesis by repressing the branch-promoting and synaptogenesis-inhibiting activities of LIN-14. ..
  34. Liu Z, Kirch S, Ambros V. The Caenorhabditis elegans heterochronic gene pathway controls stage-specific transcription of collagen genes. Development. 1995;121:2471-8 pubmed
    ..These findings indicate that the heterochronic gene pathway regulates the timing of hypodermal cell terminal differentiation by regulating larval- and adult-specific gene expression, perhaps by the direct action of lin-29. ..
  35. Arasu P, Wightman B, Ruvkun G. Temporal regulation of lin-14 by the antagonistic action of two other heterochronic genes, lin-4 and lin-28. Genes Dev. 1991;5:1825-33 pubmed
    ..Switching off lin-14 expression during the L1 stage is not triggered by the passage of time per se but, rather, is normally dependent on feeding or the feeding-dependent initiation of postembryonic cell division. ..
  36. Ruvkun G, Wightman B, Ha I. The 20 years it took to recognize the importance of tiny RNAs. Cell. 2004;116:S93-6, 2 p following S96 pubmed
  37. Pasquinelli A, Reinhart B, Slack F, Martindale M, Kuroda M, Maller B, et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature. 2000;408:86-9 pubmed
    ..elegans and Drosophila, at 48 hours after fertilization in zebrafish, and in adult stages of annelids and molluscs. The let-7 regulatory RNA may control late temporal transitions during development across animal phylogeny. ..
  38. Bettinger J, Lee K, Rougvie A. Stage-specific accumulation of the terminal differentiation factor LIN-29 during Caenorhabditis elegans development. Development. 1996;122:2517-27 pubmed
    ..LIN-29 also accumulates stage-specifically in the nuclei of a variety of non-hypodermal cells during development. Its accumulation is dependent upon the upstream heterochronic genes in some, but not all, of these non-hypodermal cells. ..
  39. Kim D, GrĂ¼n D, van Oudenaarden A. Dampening of expression oscillations by synchronous regulation of a microRNA and its target. Nat Genet. 2013;45:1337-44 pubmed publisher
    ..We propose that such a miRNA-mediated incoherent feed-forward loop is a potent filter that prevents the propagation of potentially deleterious fluctuations in gene expression during the development of an organism. ..
  40. Liu Z, Ambros V. Heterochronic genes control the stage-specific initiation and expression of the dauer larva developmental program in Caenorhabditis elegans. Genes Dev. 1989;3:2039-49 pubmed
    ..Our results further suggest that dauer larva morphogenesis by hypodermal cells requires that lin-28 acts to inhibit lin-29 during early larval stages. ..
  41. Sulston J, Horvitz H. Abnormal cell lineages in mutants of the nematode Caenorhabditis elegans. Dev Biol. 1981;82:41-55 pubmed
  42. Ferguson E, Horvitz H. Identification and characterization of 22 genes that affect the vulval cell lineages of the nematode Caenorhabditis elegans. Genetics. 1985;110:17-72 pubmed
    ..Our results suggest that we may have identified most, or all, genes of these two classes...