Cervantes Marlene, Forné Ignasi, Ranjit Suman, Gratton Enrico, Imhof Axel, Sassone-Corsi Paolo
Center for Epigenetics and Metabolism, U1233 INSERM, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Protein Analysis Unit, Biomedical Center, Ludwig Maximilian University of Munich, Munich 80539, Germany.
iScience. 2020 Jun 26;23(6):101151. doi: 10.1016/j.isci.2020.101151. Epub 2020 May 12.
The 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.
转录因子BMAL1是生物钟的核心元件，有助于对RNA聚合酶II转录的基因进行周期性调控。通过生化细胞分级分离和免疫荧光分析，我们揭示了BMAL1以前未被描述的核仁定位。我们采用无偏见的方法，通过质谱法确定BMAL1相互作用组，并将NOP58鉴定为突出的核仁相互作用蛋白。NOP58是盒C/D小核仁核糖核蛋白复合体的核心成分，与Snord118结合以控制特定的前核糖体RNA（pre-rRNA）加工步骤。这些结果表明BMAL1在核糖体RNA调控中具有非经典作用。事实上，我们表明BMAL1控制与NOP58相关的Snord118核仁水平以及独特的前rRNA中间体的切割。我们的研究结果确定了BMAL1在核仁中的一个意想不到的功能，该功能似乎与其在生物钟系统中的经典作用不同。
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