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Letters to Nature

Nature 421, 948-952 (27 February 2003) | doi:10.1038/nature01427; Received 22 October 2002; Accepted 13 January 2003

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Role for antisense RNA in regulating circadian clock function in Neurospora crassa

Cas Kramer1, Jennifer J. Loros2,3, Jay C. Dunlap3 & Susan K. Crosthwaite1

  1. School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK
  2. Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
  3. Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire 03755, USA

Correspondence to: Susan K. Crosthwaite1 Correspondence and requests for materials should be addressed to S.K.C. (e-mail: Email: susan.k.crosthwaite@man.ac.uk).

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The prevalence of antisense RNA in eukaryotes is not known and only a few naturally occurring antisense transcripts have been assigned a function1, 2, 3, 4. However, the recent identification of a large number of putative antisense transcripts5 strengthens the view that antisense RNAs might affect a wider variety of processes than previously thought. Here we show that in the model organism Neurospora crassa entrainment of the circadian clock, which is critical for the correct temporal expression of genes and their products, is controlled partly by an antisense RNA arising from a clock component locus. In a wild-type strain, levels of antisense frequency (frq) transcripts cycle in antiphase to sense frq transcripts in the dark, and are inducible by light. In mutant strains in which the induction of antisense frq RNA by light is abolished, the time of the internal clock is delayed relative to the wild-type strain, and resetting of the clock by light is altered. These data provide an unexpected link between antisense RNA and circadian timing and provide a new example of a eukaryotic cellular process regulated by naturally occurring antisense RNA.