ZNFX-1 Functions within Perinuclear Nuage to Balance Epigenetic Signals
RNA Therapeutics Institute; Program in Bioinformatics and Integrative Biology
Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Genetic Phenomena | Genetics and Genomics | Nucleic Acids, Nucleotides, and Nucleosides
Animal cells have a remarkable capacity to adopt durable and heritable gene expression programs or epigenetic states that define the physical properties and diversity of somatic cell types. The maintenance of epigenetic programs depends on poorly understood pathways that prevent gain or loss of inherited signals. In the germline, epigenetic factors are enriched in liquid-like perinuclear condensates called nuage. Here, we identify the deeply conserved helicase-domain protein, ZNFX-1, as an epigenetic regulator and component of nuage that interacts with Argonaute systems to balance epigenetic inheritance. Our findings suggest that ZNFX-1 promotes the 3' recruitment of machinery that propagates the small RNA epigenetic signal and thus counteracts a tendency for Argonaute targeting to shift 5' along the mRNA. These functional insights support the idea that recently identified subdomains of nuage, including ZNFX-1 granules or "Z-granules," may define spatial and temporal zones of molecular activity during epigenetic regulation.
Argonaute, C. elegans, CSR-1, P-granule, PIWI, RNAa, RNAe, RdRP, ZNFX-1, nuage
DOI of Published Version
Mol Cell. 2018 May 17;70(4):639-649.e6. doi: 10.1016/j.molcel.2018.04.009. Link to article on publisher's site
Ishidate, Takao; Ozturk, Ahmet R.; Durning, Daniel J.; Sharma, Rita; Shen, En-Zhi; Chen, Hao; Seth, Meetu; Shirayama, Masaki; and Mello, Craig C., "ZNFX-1 Functions within Perinuclear Nuage to Balance Epigenetic Signals" (2018). RNA Therapeutics Institute Publications. 51.