Abteilung für Molekulare Genetik, Institut für Mikrobiologie und Genetik, Göttinger Zentrum für Molekulare Biowissenschaften (GZMB), Georg-August Universität Göttingen, 37077 Göttingen, Germany.
1] Abteilung für Molekulare Genetik, Institut für Mikrobiologie und Genetik, Göttinger Zentrum für Molekulare Biowissenschaften (GZMB), Georg-August Universität Göttingen, 37077 Göttingen, Germany [2] Institut für Genomforschung und Systembiologie, Universität Bielefeld, 33615 Bielefeld, Germany.
Nat Commun. 2014;5:3123. doi: 10.1038/ncomms4123.
Eukaryotic cells have to prevent the export of unspliced pre-mRNAs until intron removal is completed to avoid the expression of aberrant and potentially harmful proteins. Only mature mRNAs associate with the export receptor Mex67/TAP and enter the cytoplasm. Here we show that the two shuttling serine/arginine (SR)-proteins Gbp2 and Hrb1 are key surveillance factors for the selective export of spliced mRNAs in yeast. Their absence leads to the significant leakage of unspliced pre-mRNAs into the cytoplasm. They bind to pre-mRNAs and the spliceosome during splicing, where they are necessary for the surveillance of splicing and the stable binding of the TRAMP complex to spliceosome-bound transcripts. Faulty transcripts are marked for their degradation at the nuclear exosome. On correct mRNAs the SR proteins recruit Mex67 upon completion of splicing to allow a quality controlled nuclear export. Altogether, these data identify a role for shuttling SR proteins in mRNA surveillance and nuclear mRNA quality control.
真核细胞必须防止未剪接的前体 mRNA 输出，直到内含子去除完成，以避免表达异常和潜在有害的蛋白质。只有成熟的 mRNA 才能与输出受体 Mex67/TAP 结合并进入细胞质。在这里，我们表明，两种穿梭的丝氨酸/精氨酸 (SR) 蛋白 Gbp2 和 Hrb1 是酵母中剪接 mRNA 选择性输出的关键监控因子。它们的缺失会导致大量未剪接的前体 mRNA 泄漏到细胞质中。它们在剪接过程中与前体 mRNA 和剪接体结合，在那里它们对于剪接的监控和 TRAMP 复合物与剪接体结合的转录本的稳定结合是必需的。有缺陷的转录本在核 exosome 处被标记进行降解。在正确的 mRNA 上，SR 蛋白在剪接完成后招募 Mex67，以允许进行质量控制的核输出。总之，这些数据确定了穿梭 SR 蛋白在 mRNA 监控和核 mRNA 质量控制中的作用。
