Abstract
Biological rhythms play a fundamental role in the physiology and behavior of most living organisms. Rhythmic circadian expression of clock-controlled genes is orchestrated by a molecular clock that relies on interconnected negative feedback loops of transcription regulators. Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation. Moreover, the circadian oscillator directly regulates the transcription of ribosomal protein mRNAs and ribosomal RNAs. Thus the circadian clock exerts a major role in coordinating transcription and translation steps underlying ribosome biogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ARNTL Transcription Factors / genetics
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Animals
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Circadian Clocks / genetics*
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Circadian Clocks / physiology
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Circadian Rhythm / genetics*
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Circadian Rhythm / physiology
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Cryptochromes / genetics
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Enzyme Activation / genetics
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Eukaryotic Initiation Factors / biosynthesis*
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Expression Regulation
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Mechanistic Target of Rapamycin Complex 1
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Multiprotein Complexes / metabolism
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Pol1 Transcription Initiation Complex Proteins / biosynthesis
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Pol1 Transcription Initiation Complex Proteins / genetics
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Protein Biosynthesis
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Proto-Oncogene Proteins c-akt / metabolism
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RNA, Messenger / biosynthesis*
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RNA, Ribosomal / biosynthesis
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Ribosomes / metabolism*
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Signal Transduction
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TOR Serine-Threonine Kinases / metabolism
Substances
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ARNTL Transcription Factors
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Bmal1 protein, mouse
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Cry1 protein, mouse
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Cry2 protein, mouse
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Cryptochromes
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Eukaryotic Initiation Factors
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Multiprotein Complexes
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Pol1 Transcription Initiation Complex Proteins
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RNA, Messenger
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RNA, Ribosomal
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transcription factor UBF
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Mechanistic Target of Rapamycin Complex 1
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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Extracellular Signal-Regulated MAP Kinases