Abstract
SummaryThe transcription factor BMAL1 is a core element of the circadian clock that contributes to cyclic control of genes transcribed by RNA polymerase II. By using biochemical cellular fractionation and immunofluorescence analyses we reveal a previously uncharacterized nucleolar localization for BMAL1. We used an unbiased approach to determine the BMAL1 interactome by mass spectrometry and identified NOP58 as a prominent nucleolar interactor. NOP58, a core component of the box C/D small nucleolar ribonucleoprotein complex, associates with Snord118 to control specific pre-ribosomal RNA (pre-rRNA) processing steps. These results suggest a non-canonical role of BMAL1 in ribosomal RNA regulation. Indeed, we show that BMAL1 controls NOP58-associated Snord118 nucleolar levels and cleavage of unique pre-rRNA intermediates. Our findings identify an unsuspected function of BMAL1 in the nucleolus that appears distinct from its canonical role in the circadian clock system.
Highlights
A large array of biological processes follow an approximate 24-h cycle, leading to circadian rhythms controlling physiology, metabolism, and behavior
SUMMARY The transcription factor Brain and muscle ARNT-like 1 (BMAL1) is a core element of the circadian clock that contributes to cyclic control of genes transcribed by RNA polymerase II
Nucleolar protein 58 (NOP58), a core component of the box C/D small nucleolar ribonucleoprotein complex, associates with Snord118 to control specific pre-ribosomal RNA processing steps. These results suggest a non-canonical role of BMAL1 in ribosomal RNA regulation
Summary
A large array of biological processes follow an approximate 24-h cycle, leading to circadian rhythms controlling physiology, metabolism, and behavior. The circadian molecular machinery is based on transcription-translation feedback loops to maintain intrinsic intracellular daily rhythms (Eckel-Mahan and Sassone-Corsi, 2013; Zhang and Kay, 2010). Circadian locomotor output cycles kaput (CLOCK) and Brain and muscle ARNT-like 1 (BMAL1) function as transcription factors activating expression of clock-controlled genes (CCGs) by binding E-box motifs at promoters of target genes transcribed by RNA polymerase II (Partch et al, 2014). Levels of circadian regulation are provided by a variety of additional mechanisms, including epigenetic control and post-translational modifications (PTMs) such as phosphorylation, acetylation, SUMOylation, and ubiquitination of clock proteins that regulate rhythmic activity (Cardone et al, 2005; Feng and Lazar, 2012; Hirayama et al, 2007; Kondratov et al, 2003). Proper circadian control is obtained through a complex system of interplaying regulatory pathways
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