Skip to main content
SpringerLink
Log in

The role of microRNAs (miRNA) in circadian rhythmicity

  • Review Article
  • Published:
Journal of Genetics Aims and scope Submit manuscript

Abstract

MicroRNA (miRNA) is a recently discovered new class of small RNA molecules that have a significant role in regulating gene and protein expression. These small RNAs (∼22 nt) bind to 3′ untranslated regions (3′ UTRs) and induce degradation or repression of translation of their mRNA targets. Hundreds of miRNAs have been identified in various organisms and have been shown to play a significant role in development and normal cell functioning. Recently, a few studies have suggested that miRNAs may be an important regulators of circadian rhythmicity, providing a new dimension (posttranscriptional) of our understanding of biological clocks. Here, we describe the mechanisms of miRNA regulation, and recent studies attempting to identify clock miRNAs and their function in the circadian system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Akhtar R. A., Reddy A. B., Maywood E. S., Clayton J. D., King V. M., Smith A. G. et al. 2002 Circadian cycling of the mouse liver transcriptome, as revealed by cDNA microarray, is driven by the suprachiasmatic nucleus. Curr. Biol. 12, 540–550.

    Article  PubMed  CAS  Google Scholar 

  • Alabadi D., Oyama T., Yanovsky M. J., Harmon F. G., Mas P. and Kay S. A. 2001 Reciprocal regulation between TOC1 and LHY/CCA1 within the Arabidopsis circadian clock. Science 293, 880–883.

    Article  PubMed  CAS  Google Scholar 

  • Ambros V. 2004 The functions of animal microRNAs. Nature 431, 350–355.

    Article  PubMed  CAS  Google Scholar 

  • Ambros V., Bartel B., Bartel D. P., Burge C. B., Carrington J. C., Chen X. et al. 2003 A uniform system for microRNA annotation. RNA 9, 277–279.

    Article  PubMed  CAS  Google Scholar 

  • Behm-Ansmant I., Rehwinkel J., Doerks T., Stark A., Bork P. and Izaurralde E. 2006 mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes Dev. 20, 1885–1898.

    Article  PubMed  CAS  Google Scholar 

  • Bernstein E., Caudy A. A., Hammond S. M. and Hannon G. J. 2001 Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409, 363–366.

    Article  PubMed  CAS  Google Scholar 

  • Bohnsack M. T., Czaplinski K. and Gorlich D. 2004 Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 10, 185–191.

    Article  PubMed  CAS  Google Scholar 

  • Brennecke J., Stark A., Russell R. B. and Cohen S. M. 2005 Principles of microRNA-target recognition. PLoS Biol. 3, e85.

    Article  PubMed  Google Scholar 

  • Bushati N. and Cohen S. M. 2007 microRNA functions. Annu. Rev. Cell Dev. Biol. 23, 175–205.

    Article  PubMed  CAS  Google Scholar 

  • Ceriani M. F., Hogenesch J. B., Yanovsky M., Panda S., Straume M. and Kay S. A. 2002 Genome-wide expression analysis in Drosophila reveals genes controlling circadian behavior. J. Neurosci. 22, 9305–9319.

    PubMed  CAS  Google Scholar 

  • Cheng H. Y., Papp J. W., Varlamova O., Dziema H., Russell B., Curfman J. P. et al. 2007 microRNA modulation of circadianclock period and entrainment. Neuron 54, 813–829.

    Article  PubMed  CAS  Google Scholar 

  • Claridge-Chang A., Wijnen H., Naef F., Boothroyd C., Rajewsky N. and Young M. W. 2001 Circadian regulation of gene expression systems in the Drosophila head. Neuron 32, 657–671.

    Article  PubMed  CAS  Google Scholar 

  • Crosthwaite S. K. 2004 Circadian clocks and natural antisense RNA. FEBS Lett. 567, 49–54.

    Article  PubMed  CAS  Google Scholar 

  • Darlington T. K., Wager-Smith K., Ceriani M. F., Staknis D., Gekakis N., Steeves T. D. et al. 1998 Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim. Science 280, 1599–1603.

    Article  PubMed  CAS  Google Scholar 

  • Davis C. J., Bohnet S. G., Meyerson J. M. and Krueger J. M. 2007 Sleep loss changes microRNA levels in the brain: a possible mechanism for state-dependent translational regulation. Neurosci. Lett. 422, 68–73.

    Article  PubMed  CAS  Google Scholar 

  • Denli A. M., Tops B. B., Plasterk R. H., Ketting R. F. and Hannon G. J. 2004 Processing of primary microRNAs by the microprocessor complex. Nature 432, 231–235.

    Article  PubMed  CAS  Google Scholar 

  • Didiano D. and Hobert O. 2006 Perfect seed pairing is not a generally reliable predictor for miRNA-target interactions. Nat. Struct. Mol. Biol. 13, 849–851.

    Article  PubMed  CAS  Google Scholar 

  • Duffield G. E. 2003 DNA microarray analyses of circadian timing: the genomic basis of biological time. J. Neuroendocrinol. 15, 991–1002.

    Article  PubMed  CAS  Google Scholar 

  • Dunlap J. C. 1999 Molecular bases for circadian clocks. Cell 96, 271–290.

    Article  PubMed  CAS  Google Scholar 

  • Esau C., Davis S., Murray S. F., Yu X. X., Pandey S.K., Pear M. et al. 2006 miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 3, 87–98.

    Article  PubMed  CAS  Google Scholar 

  • Farh K. K., Grimson A., Jan C., Lewis B. P., Johnston W. K., Lim L. P. et al. 2005 The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science 310, 1817–1821.

    Article  PubMed  CAS  Google Scholar 

  • Gallego M. and Virshup D. M. 2007 Post-translational modifications regulate the ticking of the circadian clock. Nat. Rev. Mol. Cell Biol. 8, 139–148.

    Article  PubMed  CAS  Google Scholar 

  • Giraldez A. J., Mishima Y., Rihel J., Grocock R. J., Van Dongen S., Inoue K. et al. 2006 Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312, 75–79.

    Article  PubMed  CAS  Google Scholar 

  • Green C. B., Nicholas D., Shihoko K., Carl A. S., Joseph F., David L. et al. 2007 Loss of nocturnin, a circadian deadenylase, confers resistance to hepatic steatosis and diet-induced obesity. Proc. Natl. Acad. Sci. USA 104, 9888–9893.

    Article  PubMed  CAS  Google Scholar 

  • Griffiths-Jones S., Saini H. K., van Dongen S. and Enright A. J. 2008 miRBase: tools for microRNA genomics. Nucleic Acids Res. 36, 154–158.

    Article  Google Scholar 

  • Grimson A., Farh K. K., Johnston W. K., Garrett-Engele P., Lim L. P. and Bartel D. P. 2007 MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol. Cell 27, 91–105.

    Article  PubMed  CAS  Google Scholar 

  • Grun D., Wang Y. L., Langenberger D., Gunsalus K. C. and Rajewsky N. 2005 microRNA target predictions across seven Drosophila species and comparison to mammalian targets. PLoS Comput. Biol. 1, e13.

    Article  PubMed  Google Scholar 

  • Han S., Kim T., Ha D. and Kim K. 2005 Rhythmic expression of adenylyl cyclase VI contributes to the differential regulation of serotonin N-acetyltransferase by bradykinin in rat pineal glands. J. Biol. Chem. 280, 38228–38234.

    Article  PubMed  CAS  Google Scholar 

  • Hardin P. E., Hall J. C. and Rosbash M. 1990 Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature 343, 536–540.

    Article  PubMed  CAS  Google Scholar 

  • Hayama R. and Coupland G. 2003 Shedding light on the circadian clock and the photoperiodic control of flowering. Curr. Opin. Plant Biol. 6, 13–19.

    Article  PubMed  CAS  Google Scholar 

  • Hsu P. W. C., Huang H., Hsu S., Lin L., Tsou A., Tseng C. et al. 2006 miRNAMap: genomic maps of microRNA genes and their target genes in mammalian genomes. Nucleic Acids Res. 34, D135–139.

    Article  PubMed  CAS  Google Scholar 

  • Humphreys D. T., Westman B. J., Martin D. I. and Preiss T. 2005 MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function. Proc. Natl. Acad. Sci. USA. 102, 16961–16966.

    Article  PubMed  CAS  Google Scholar 

  • Impey S., McCorkle S. R., Cha-Molstad H., Dwyer J. M., Yochum G. S., Boss J. M. et al. 2004 Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions. Cell 119, 1041–1054.

    PubMed  CAS  Google Scholar 

  • Jung J. H., Seo Y. H., Seo P. J., Reyes J. L., Yun J., Chua N. H. et al. 2007 The GIGANTEA-regulated microRNA172 mediates photoperiodic flowering independent of CONSTANS in Arabidopsis. Plant Cell 19, 2736–2748.

    Article  PubMed  CAS  Google Scholar 

  • Karaganis S., Kumar V., Beremand P., Bailey M., Thomas T. and Cassone V. 2008 Circadian genomics of the chick pineal gland in vitro. BMC Genomics 9, 206.

    Article  PubMed  Google Scholar 

  • Keegan K. P., Pradhan S., Wang J. P. and Allada R. 2007 Metaanalysis of Drosophila circadian microarray studies identifies a novel set of rhythmically expressed genes. PLoS Comput. Biol. 3, e208.

    Article  PubMed  Google Scholar 

  • Kojima S., Gatfield D. and Green C. 2008 Nocturnin expression is regulated post-transcriptionally by miR-122. 20th meeting, Society for research on biological rhythms, Destin, Florida.

  • Kramer C., Loros J. J., Dunlap J. C. and Crosthwaite S. K. 2003 Role for antisense RNA in regulating circadian clock function in Neurospora crassa. Nature 421, 948–952.

    Article  PubMed  CAS  Google Scholar 

  • Krek A., Grun D., Poy M. N., Wolf R., Rosenberg L., Epstein E. J. et al. 2005 Combinatorial microRNA target predictions. Nat. Genet. 37, 495–500.

    Article  PubMed  CAS  Google Scholar 

  • Kume K., Zylka M. J., Sriram S., Shearman L. P., Weaver D. R., Jin X. et al. 1999 mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell 98, 193–205.

    Article  PubMed  CAS  Google Scholar 

  • Landthaler M., Yalcin A. and Tuschl T. 2004 The human DiGeorge syndrome critical region gene 8 and its D. melanogaster homolog are required for miRNA biogenesis. Curr. Biol. 14, 2162–2167.

    Article  PubMed  CAS  Google Scholar 

  • Lee K., Loros J. J. and Dunlap J. C. 2000 Interconnected feedback loops in the Neurospora circadian system. Science 289, 107–110.

    Article  PubMed  CAS  Google Scholar 

  • Lee R. C., Feinbaum R. L. and Ambros V. 1993 The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843–854.

    Article  PubMed  CAS  Google Scholar 

  • Lee Y. S., Nakahara K., Pham J. W., Kim K., He Z., Sontheimer E. J. et al. 2004 Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell 117, 69–81.

    Article  PubMed  CAS  Google Scholar 

  • Lewis B. P., Shih I. H., Jones-Rhoades M. W., Bartel D. P. and Burge C. B. 2003 Prediction of mammalian microRNA targets. Cell 115, 787–798.

    Article  PubMed  CAS  Google Scholar 

  • Lin Y., Han M., Shimada B., Wang L., Gibler T. M., Amarakone A. et al. 2002 Influence of the period-dependent circadian clock on diurnal, circadian, and aperiodic gene expression in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 99, 9562–9567.

    Article  PubMed  CAS  Google Scholar 

  • Long D., Lee R., Williams P., Chan C. Y., Ambros V. and Ding Y. 2007 Potent effect of target structure on microRNA function. Nat. Struct. Mol. Biol. 14, 287–294.

    Article  PubMed  CAS  Google Scholar 

  • Matranga C., Tomari Y., Shin C., Bartel D. P. and Zamore P. D., 2005 Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123, 607–620.

    Article  PubMed  CAS  Google Scholar 

  • McDonald M. J. and Rosbash M. 2001 Microarray analysis and organization of circadian gene expression in Drosophila. Cell 107, 567–578.

    Article  PubMed  CAS  Google Scholar 

  • Mishima Y., Giraldez A. J., Takeda Y., Fujiwara T., Sakamoto H., Schier A. F. et al. 2006 Differential regulation of germline mRNAs in soma and germ cells by zebrafish miR-430. Curr. Biol. 16, 2135–2142.

    Article  PubMed  CAS  Google Scholar 

  • Miyoshi K., Tsukumo H., Nagami T., Siomi H. and Siomi M. C. 2005 Slicer function of Drosophila argonautes and its involvement in RISC formation. Genes Dev. 19, 2837–2848.

    Article  PubMed  CAS  Google Scholar 

  • Mizoguchi T., Wright L., Fujiwara S., Cremer F., Lee K., Onouchi H. et al. 2005 Distinct roles of GIGANTEA in promoting flowering and regulating circadian rhythms in Arabidopsis. Plant Cell 17, 2255–2270.

    Article  PubMed  CAS  Google Scholar 

  • Nottrott S., Simard M. J. and Richter J. D. 2006 Human let-7a miRNA blocks protein production on actively translating polyribosomes. Nat. Struct. Mol. Biol. 13, 1108–1114.

    Article  PubMed  CAS  Google Scholar 

  • Panda S., Antoch M. P., Miller B. H., Su A. I., Schook A. B., Straume M. et al. 2002 Coordinated transcription of key pathways in the mouse by the circadian clock. Cell 109, 307–320.

    Article  PubMed  CAS  Google Scholar 

  • Petersen C. P., Bordeleau M. E., Pelletier J. and Sharp P. A. 2006 Short RNAs repress translation after initiation in mammalian cells. Mol. Cell 21, 533–542.

    Article  PubMed  CAS  Google Scholar 

  • Pillai R. S., Bhattacharyya S. N., Artus C. G., Zoller T., Cougot N., Basyuk E. et al. 2005 Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science 309, 1573–1576.

    Article  PubMed  CAS  Google Scholar 

  • Rajewsky N. 2006 microRNA target predictions in animals. Nat. Genet. 38, 8–13.

    Article  Google Scholar 

  • Rana T. M. 2007 Illuminating the silence: understanding the structure and function of small RNAs. Nat. Rev. Mol. Cell Biol. 8, 23–36.

    Article  PubMed  CAS  Google Scholar 

  • Reddy A. B., Karp N. A., Maywood E. S., Sage E. A., Deery M., O’Neill J. S. et al. 2006 Circadian orchestration of the hepatic proteome. Curr. Biol. 16, 1107–1115.

    Article  PubMed  CAS  Google Scholar 

  • Samach A. and Coupland G. 2000 Time measurement and the control of flowering in plants. Bioessays 22, 38–47.

    Article  PubMed  CAS  Google Scholar 

  • Schmid M., Uhlenhaut N. H., Godard F., Demar M., Bressan R., Weigel D. et al. 2003 Dissection of floral induction pathways using global expression analysis. Development 130, 6001–6012.

    Article  PubMed  CAS  Google Scholar 

  • Shende V. R., Beremand P. D. and Cassone V. M. 2008 MicroRNA rhythms in the chick pineal gland. 20th meeting, Society for research on biological rhythms, Destin, Florida.

  • Stark A., Brennecke J., Bushati N., Russell R. B. and Cohen S. M. 2005 Animal microRNAs confer robustness to gene expression and have a significant impact on 3′UTR evolution. Cell 123, 1133–1146.

    Article  PubMed  CAS  Google Scholar 

  • Storch K., Lipan O., Leykin I., Viswanathan N., Davis F. C., Wong W. H. et al. 2002 Extensive and divergent circadian gene expression in liver and heart. Nature 417, 78–83.

    Article  PubMed  CAS  Google Scholar 

  • Ueda H. R., Matsumoto A., Kawamura M., Iino M., Tanimura T. and Hashimoto S. 2002 Genome-wide transcriptional orchestration of circadian rhythms in Drosophila. J. Biol. Chem. 277, 14048–14052.

    Article  PubMed  CAS  Google Scholar 

  • Vasudevan S., Tong Y. and Steitz J. A. 2007 Switching from repression to activation: microRNAs can up-regulate translation. Science 318, 1931–1934.

    Article  PubMed  CAS  Google Scholar 

  • Vella M. C., Choi E. Y., Lin S. Y., Reinert K. and Slack F. J. 2004a The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from the lin-41 3′UTR. Genes Dev. 18, 132–137.

    Article  PubMed  CAS  Google Scholar 

  • Vella M. C., Reinert K. and Slack F. J. 2004b Architecture of a validated microRNA::target interaction. Chem. Biol. 11, 1619–1623.

    Article  PubMed  CAS  Google Scholar 

  • Wightman B., Ha I. and Ruvkun G. 1993 Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75, 855–862.

    Article  PubMed  CAS  Google Scholar 

  • Wu L., Fan J. and Belasco J. G. 2006 MicroRNAs direct rapid deadenylation of mRNA. Proc. Natl. Acad. Sci. USA 103, 4034–4039.

    Article  PubMed  CAS  Google Scholar 

  • Xu S., Witmer P. D., Lumayag S., Kovacs B. and Valle D. 2007 MicroRNA (miRNA) transcriptome of mouse retina and identification of a sensory organ-specific miRNA cluster. J. Biol. Chem. 282, 25053–25066.

    Article  PubMed  CAS  Google Scholar 

  • Yang M., Lee J. E., Padgett R. W. and Edery I. 2008 Circadian regulation of a limited set of conserved microRNAs in Drosophila. BMC Genomics 9, 83.

    Article  PubMed  Google Scholar 

  • Yanovsky M. J. and Kay S. A. 2003 Living by the calendar: how plants know when to flower. Nat. Rev. Mol. Cell Biol. 4, 265–275.

    Article  PubMed  CAS  Google Scholar 

  • Zheng X. and Sehgal A. 2008 Probing the relative importance of molecular oscillations in the circadian clock. Genetics 178, 1147–1155.

    Article  PubMed  CAS  Google Scholar 

  • Zuker M. 2003 Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 31, 3406–3415.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Genetics, University of Leicester, University Road, Leicester, LE1 7RH, UK

    Mirko Pegoraro & Eran Tauber

Authors
  1. Mirko Pegoraro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eran Tauber
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eran Tauber.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pegoraro, M., Tauber, E. The role of microRNAs (miRNA) in circadian rhythmicity. J Genet 87, 505–511 (2008). https://doi.org/10.1007/s12041-008-0073-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12041-008-0073-8

Keywords

Search

Navigation