Molecular mechanism of temperature sensing by the circadian clock of Neurospora crassa.
Expression levels and ratios of the long (l) and short (s) isoforms of the Neurospora circadian clock protein FREQUENCY (FRQ) are crucial for temperature compensation of circadian rhythms. We show that the ratio of l-FRQ versus s-FRQ is regulated by thermosensitive splicing of intron 6 of frq, a process removing the translation initiation site of l-FRQ. Thermosensitivity is due to inefficient recognition of nonconsensus splice sites at elevated temperature. The temperature-dependent accumulation of FRQ relative to bulk protein is controlled at the level of translation. The 5'-UTR of frq RNA contains six upstream open reading frames (uORFs) that are in nonconsensus context for translation initiation. Thermosensitive trapping of scanning ribosomes at the uORFs leads to reduced translation of the main ORF and allows adjustment of FRQ levels according to ambient temperature.
Diernfellner
Axel C R
AC
Biochemistry Center, University of Heidelberg (BZH), Heidelberg D-69120, Germany.
Schafmeier
Tobias
T
Merrow
Martha W
MW
Brunner
Michael
M
D020121:5' Untranslated Regions; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D004271:DNA, Fungal / Q000235:genetics; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D005800:Genes, Fungal; D017344:Genes, Insect; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D009492:Neurospora crassa / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics; D016366:Open Reading Frames; D056950:Period Circadian Proteins; D012331:RNA, Fungal / Q000235:genetics; D013696:Temperature
D020121:5' Untranslated Regions; D004271:DNA, Fungal; D029721:Drosophila Proteins; C087405:FRQ protein, Neurospora crassa; D005656:Fungal Proteins; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; D012331:RNA, Fungal