Creative Research Initiatives Center for Molecular Biology of Translation, Korea University, Seoul 02841, Republic of Korea.
Division of Life Sciences, Korea University, Seoul 02841, Republic of Korea.
Nucleic Acids Res. 2021 Aug 20;49(14):8261-8276. doi: 10.1093/nar/gkab579.
Newly synthesized mRNA is translated during its export through the nuclear pore complex, when its 5'-cap structure is still bound by the nuclear cap-binding complex (CBC), a heterodimer of cap-binding protein (CBP) 80 and CBP20. Despite its critical role in mRNA surveillance, the mechanism by which CBC-dependent translation (CT) is regulated remains unknown. Here, we demonstrate that the CT initiation factor (CTIF) is tethered in a translationally incompetent manner to the perinuclear region by the DEAD-box helicase 19B (DDX19B). DDX19B hands over CTIF to CBP80, which is associated with the 5'-cap of a newly exported mRNA. The resulting CBP80-CTIF complex then initiates CT in the perinuclear region. We also show that impeding the interaction between CTIF and DDX19B leads to uncontrolled CT throughout the cytosol, consequently dysregulating nonsense-mediated mRNA decay. Altogether, our data provide molecular evidence supporting the importance of tight control of local translation in the perinuclear region.
新合成的 mRNA 在通过核孔复合物输出时进行翻译，此时其 5' - 帽结构仍被核帽结合复合物（CBC）结合，CBC 是帽结合蛋白（CBP）80 和 CBP20 的异二聚体。尽管 CBC 依赖性翻译（CT）在 mRNA 监测中具有关键作用，但调节 CT 的机制仍不清楚。在这里，我们证明 CT 起始因子（CTIF）通过 DEAD 盒解旋酶 19B（DDX19B）以翻译无能力的方式被束缚在核周区域。DDX19B 将 CTIF 移交给与新输出 mRNA 的 5' - 帽相关的 CBP80。由此产生的 CBP80-CTIF 复合物随后在核周区域启动 CT。我们还表明，阻碍 CTIF 和 DDX19B 之间的相互作用会导致整个细胞质中不受控制的 CT，从而导致无意义介导的 mRNA 降解失调。总之，我们的数据提供了分子证据，支持核周区域局部翻译严格控制的重要性。
