Dynamic FMR1 granule phase switch instructed by m6A modification contributes to maternal RNA decay

• DOI: 10.1038/s41467-022-28547-7
• Publication Date: 2022-02-14T11:12:29Z
• Authors: Guoqiang Zhang; Yongru Xu; Xiaona Wang; Yuanxiang Zhu; Liangliang Wang; Wenxin Zhang; Yiru Wang; Yajie Gao; Xuna Wu; Ying Cheng; Qinmiao Sun; Dahua Chen
• Keywords: FMR1; Granule (geology); Stress granule; Ribonucleoprotein particle

Abstract Maternal RNA degradation is critical for embryogenesis and tightly controlled by maternal RNA-binding proteins. Fragile X mental-retardation protein (FMR1) binds target mRNAs to form ribonucleoprotein (RNP) complexes/granules that control various biological processes, including early embryogenesis. However, how FMR1 recognizes FMR1-RNP granule assembly/disassembly regulates FMR1-associated remain elusive. Here we show Drosophila preferentially containing m6A-marked “AGACU” motif with high affinity contributes degradation. The high-affinity binding largely depends on a hydrophobic network within KH2 domain. Importantly, this greatly induces condensation efficiently recruit unmodified mRNAs. of then causes de-condensation, allowing normal Our findings reveal sequence-specific instruct granules undergo dynamic phase-switch, thus mRNA decay. This mechanism may represent general principle regulated RNP-granules processing development.