A DNA methylation reader complex regulates rRNA gene expression

Ren, Gou, Zhuo, Chen et al. revealed that a DNA methylation reader complex recruits an effector protein to regulate variant-specific 45S rRNA silencing.


By Weiqiang Qian, Peking University

Background: Eukaryotic genomes harbor thousands of 45S ribosomal RNA (rRNA) genes that are tandemly arrayed at nucleolus organizer regions (NORs). Some of these rRNA genes are silenced during development. For instance, NOR2 is silenced a few days after germination in Arabidopsis (Arabidopsis thaliana). Selective rRNA gene silencing is thought to be a manifestation of rRNA gene dosage control, a mechanism that controls the number of active rRNA genes to meet the physiological needs of the cell.

Question: Growing evidence has revealed that DNA methylation is involved in selective 45S rRNA gene silencing in both plants and animals. However, the molecular mechanisms that act downstream of DNA methylation to silence specific rRNA gene variants in Arabidopsis remain unclear.

Findings: In this study, we investigated the DNA methylation readers and effectors involved in selective rRNA gene silencing. We found that a protein complex, consisting of METHYL-CpG-BINDING DOMAIN PROTEIN5 (MBD5), MBD6, and two α-crystallin domain-containing proteins, ACD15.5 and ACD21.4, reads DNA methylation to silence specific 45S rRNA gene variants. The complex directly binds to 45S rDNA through phase separation. The four proteins in this complex are interdependent for their phase separation and function. We further demonstrated that MICRORCHIDIA6 (MORC6) is an effector that is recruited to 45S rDNA regions by the MBD–ACD complex for selective 45S rRNA silencing. Our results reveal a mechanism that functions downstream of DNA methylation to achieve selective 45S rRNA gene silencing in plants.

Next steps: We are working on elucidating the molecular mechanism underlying MORC6-mediated selective rRNA gene silencing. We will determine DNA methylation levels of 45S rRNA genes and detect NOR structures in morc6 mutants.


Zhitong Ren, Runyu Gou, Wanqing Zhuo, Zhiyu Chen, Xiaochang Yin, Yuxin Cao, Yue Wang, Yingjie Mi, Yannan Liu, Yingxiang Wang, Liu-Min Fan, Xing Wang Deng and Weiqiang Qian. (2024). The MBD–ACD DNA methylation reader complex recruits MICRORCHIDIA6 to regulate rRNA gene expression in Arabidopsis. https://doi.org/10.1093/plcell/koad313