Letter | Published:

MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode

Nature volume 430, pages 785789 (12 August 2004) | Download Citation



Animal microRNAs (miRNAs) are gene regulatory factors that prevent the expression of specific messenger RNA targets by binding to their 3′ untranslated region1,2,3. The Caenorhabditis elegans lsy-6 miRNA (for lateral symmetry defective) is required for the left/right asymmetric expression of guanyl cyclase (gcy) genes in two chemosensory neurons termed ASE left (ASEL) and ASE right (ASER)4,5. The asymmetric expression of these putative chemoreceptors in turn correlates with the functional lateralization of the ASE neurons6. Here we find that a mutation in the die-1 zinc-finger transcription factor disrupts both the chemosensory laterality and left/right asymmetric expression of chemoreceptor genes in the ASE neurons. die-1 controls chemosensory laterality by activating the expression of lsy-6 specifically in ASEL, but not in ASER, where die-1 expression is downregulated through two sites in its 3′ untranslated region. These two sites are complementary to mir-273, a previously uncharacterized miRNA, whose expression is strongly biased towards ASER. Forced bilateral expression of mir-273 in ASEL and ASER causes a loss of asymmetric die-1 expression and ASE laterality. Thus, an inverse distribution of two sequentially acting miRNAs in two bilaterally symmetric neurons controls laterality of the nematode chemosensory system.

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We thank C. Antonio for the ot100 allele, J.Hardin for die-1 reagents, Q. Chen and S. Narula for expert technical assistance, J. Tien for help with mapping ot26, I. Greenwald for advice, L. Johnston, A. Lanjuin, P. Sengupta, I. Greenwald and F. Slack for reading the manuscript. S.C. was funded by an NIH predoctoral fellowship, R.J.J. by an NSF predoctoral fellowship, and C.F.-J. by a American Heart Association predoctoral fellowship. O.H. was supported by grants from the NIH, the McKnight Foundation and the Irma T.Hirschl Trust.

Author information


  1. Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University Medical Center, 701 W. 168th Street, New York 10032, USA

    • Sarah Chang
    • , Robert J. Johnston Jr
    •  & Oliver Hobert
  2. Institute of Neuroscience, University of Oregon, Eugene, Oregon 97403, USA

    • Christian Frøkjær-Jensen
    •  & Shawn Lockery


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Competing interests

The authors declare that they have no competing financial interests.

Corresponding author

Correspondence to Oliver Hobert.

Supplementary information

Word documents

  1. 1.

    Supplementary Data

    This file contains additional Methods, references and legends to Supplementary

Image files

  1. 1.

    Supplementary Figure 1

    ot26 is an allele of the Zn finger transcription factor DIE-1 which acts in ASE to affect gcy gene expression.

  2. 2.

    Supplementary Figure 2

    die-1 controls lim-6 expression.

  3. 3.

    Supplementary Figure 3

    Identification of mir-273 complementary sites and the structure of the mir-273 precursor.

  4. 4.

    Supplementary Figure 4

    Bilateral expression of mir-273 disrupts ASE laterality.

  5. 5.

    Supplementary Table 1

  6. 6.

    Supplementary Table 2

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