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

Abstract

The prevalence of antisense RNA in eukaryotes is not known and only a few naturally occurring antisense transcripts have been assigned a function. However, the recent identification of a large number of putative antisense transcripts 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.

The role of microRNAs (miRNA) in circadian rhythmicity

“…This was elegantly demonstrated using mutant strains where the expression of the antisense, which is normally light-induced, is abolished. In these strains, circadian rhythmicity was delayed and phase response to light pulses was dramatically enhanced compared with the response of the wild-type (Kramer et al 2003).…”

“…For example, in Neurospora, several (5-5.5 kb) antisense frequency (frq) RNA are present (Kramer et al 2003) which completely overlap with the sense transcript. The levels of the frq antisense RNAs cycle in antiphase with the sense frq RNA under free-running conditions, suggesting that the frq-antisense transcript has a clock function.…”

Aging in the circadian system: Considerations for health, disease prevention and longevity

“…Similarly, the transcription factor DPB is positively regulated by the CLOCK:BMAL1 complex (Ripperger and Schibler, 2006) and acts as an important output mechanism by driving rhythmic transcription of other output genes via a PAR basic leucine zipper (PAR bZIP) (Lavery et al, 1999). Whereas most work to date has focused on transcriptional regulation as the key mechanism driving cellular rhythms, post-transcriptional and post-translational events are also critical for circadian coordination (Baggs and Green, 2003;Kramer et al, 2003;Reddy et al, 2006).…”

The frequency natural antisense transcript first promotes, then represses, frequency gene expression via facultative heterochromatin

“…The frq locus is composed of three transcripts: the frq gene encoding FRQ protein (6), a natural antisense transcript (NAT) qrf (frq spelled backwards) (18), and a small upstream transcript of unknown function that spans the clock box (c-box) promoter element ( Fig. 1 A and B).…”