Synthetic and Functional Biomolecules Center, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Beijing National Laboratory for Molecular Sciences, Peking University, Beijing, 100871, China.
Peking-Tsinghua Center for Life Sciences, Beijing, 100871, China.
Genome Biol. 2023 Apr 30;24(1):103. doi: 10.1186/s13059-023-02947-4.
RNA N-methyladenosine (mA) modification is critical for plant growth and crop yield. mA reader proteins can recognize mA modifications to facilitate the functions of mA in gene regulation. ECT2, ECT3, and ECT4 are mA readers that are known to redundantly regulate trichome branching and leaf growth, but their molecular functions remain unclear.
Here, we show that ECT2, ECT3, and ECT4 directly interact with each other in the cytoplasm and perform genetically redundant functions in abscisic acid (ABA) response regulation during seed germination and post-germination growth. We reveal that ECT2/ECT3/ECT4 promote the stabilization of their targeted mA-modified mRNAs, but have no function in alternative polyadenylation and translation. We find that ECT2 directly interacts with the poly(A) binding proteins, PAB2 and PAB4, and maintains the stabilization of mA-modified mRNAs. Disruption of ECT2/ECT3/ECT4 destabilizes mRNAs of ABA signaling-related genes, thereby promoting the accumulation of ABI5 and leading to ABA hypersensitivity.
Our study reveals a unified functional model of mA mediated by mA readers in plants. In this model, ECT2/ECT3/ECT4 promote stabilization of their target mRNAs in the cytoplasm.
RNA N6-甲基腺苷(m6A)修饰对于植物生长和作物产量至关重要。m6A 阅读蛋白可以识别 m6A 修饰,从而促进 m6A 在基因调控中的功能。ECT2、ECT3 和 ECT4 是已知冗余调节毛状体分支和叶片生长的 m6A 阅读蛋白,但它们的分子功能仍不清楚。
在这里,我们表明 ECT2、ECT3 和 ECT4 在细胞质中直接相互作用,并在种子萌发和萌发后生长过程中的脱落酸(ABA)响应调节中发挥遗传冗余功能。我们揭示 ECT2/ECT3/ECT4 促进其靶向 m6A 修饰的 mRNA 的稳定性,但在可变多聚腺苷酸化和翻译中没有功能。我们发现 ECT2 直接与多聚(A)结合蛋白 PAB2 和 PAB4 相互作用,并维持 m6A 修饰的 mRNA 的稳定性。ECT2/ECT3/ECT4 的破坏使 ABA 信号相关基因的 mRNA 不稳定,从而促进 ABI5 的积累,导致 ABA 超敏反应。
我们的研究揭示了植物中 m6A 阅读蛋白介导的 m6A 统一功能模型。在这个模型中,ECT2/ECT3/ECT4 促进其靶 mRNA 在细胞质中的稳定性。