State Key Laboratory for Crop Genetics & Germplasm Enhancement and Utilization, Zhongshan Biological Breeding Laboratory, National Observation and Research Station of Rice Germplasm Resources, Nanjing Agricultural University, Nanjing 210095, China; State Key Laboratory for Crop Gene Resources and Breeding, Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking-Tsinghua Center for Life Sciences, Beijing Advanced Center of RNA Biology, Peking University, Beijing, China.
Mol Plant. 2024 Jun 3;17(6):935-954. doi: 10.1016/j.molp.2024.05.002. Epub 2024 May 7.
N-Methyladenosine (mA) is one of the most abundant modifications of eukaryotic mRNA, but its comprehensive biological functionality remains further exploration. In this study, we identified and characterized a new flowering-promoting gene, EARLY HEADING DATE6 (EHD6), in rice. EHD6 encodes an RNA recognition motif (RRM)-containing RNA binding protein that is localized in the non-membranous cytoplasm ribonucleoprotein (RNP) granules and can bind both mA-modified RNA and unmodified RNA indiscriminately. We found that EHD6 can physically interact with YTH07, a YTH (YT521-B homology) domain-containing mA reader. We showed that their interaction enhances the binding of an mA-modified RNA and triggers relocation of a portion of YTH07 from the cytoplasm into RNP granules through phase-separated condensation. Within these condensates, the mRNA of a rice flowering repressor, CONSTANS-like 4 (OsCOL4), becomes sequestered, leading to a reduction in its protein abundance and thus accelerated flowering through the Early heading date 1 pathway. Taken together, these results not only shed new light on the molecular mechanism of efficient mA recognition by the collaboration between an RNA binding protein and YTH family mA reader, but also uncover the potential for mA-mediated translation regulation through phase-separated ribonucleoprotein condensation in rice.
N6-甲基腺苷（m6A）是真核 mRNA 中最丰富的修饰之一，但它的全面生物学功能仍有待进一步探索。在这项研究中，我们在水稻中鉴定和表征了一个新的促进开花的基因，EARLY HEADING DATE6（EHD6）。EHD6 编码一个含有 RNA 识别基序（RRM）的 RNA 结合蛋白，该蛋白定位于非膜细胞质核糖核蛋白（RNP）颗粒中，可以非特异性地结合 m6A 修饰的 RNA 和未修饰的 RNA。我们发现 EHD6 可以与 YTH07 发生物理相互作用，YTH07 是一个含有 YTH（YT521-B 同源）结构域的 m6A 阅读器。我们表明，它们的相互作用增强了 m6A 修饰 RNA 的结合，并通过相分离浓缩触发一部分 YTH07 从细胞质转移到 RNP 颗粒中。在这些浓缩物中，水稻开花抑制剂 CONSTANS-like 4（OsCOL4）的 mRNA 被隔离，导致其蛋白丰度降低，从而通过 Early heading date 1 途径加速开花。总之，这些结果不仅揭示了 RNA 结合蛋白和 YTH 家族 m6A 阅读器之间的协作对高效 m6A 识别的分子机制，还揭示了 m6A 通过相分离核糖核蛋白凝聚在水稻中进行翻译调控的潜力。
