Abteilung für Molekulare Genetik, Institut für Mikrobiologie und Genetik, Göttinger Zentrum für Molekulare Biowissenschaften (GZMB), Georg-August Universität Göttingen, Göttingen, Germany.
NGS-Integrative Genomics Core Unit, Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany.
Nature. 2024 Jul;631(8020):432-438. doi: 10.1038/s41586-024-07576-w. Epub 2024 Jun 19.
When mRNAs have been transcribed and processed in the nucleus, they are exported to the cytoplasm for translation. This export is mediated by the export receptor heterodimer Mex67-Mtr2 in the yeast Saccharomyces cerevisiae (TAP-p15 in humans). Interestingly, many long non-coding RNAs (lncRNAs) also leave the nucleus but it is currently unclear why they move to the cytoplasm. Here we show that antisense RNAs (asRNAs) accelerate mRNA export by annealing with their sense counterparts through the helicase Dbp2. These double-stranded RNAs (dsRNAs) dominate export compared with single-stranded RNAs (ssRNAs) because they have a higher capacity and affinity for the export receptor Mex67. In this way, asRNAs boost gene expression, which is beneficial for cells. This is particularly important when the expression program changes. Consequently, the degradation of dsRNA, or the prevention of its formation, is toxic for cells. This mechanism illuminates the general cellular occurrence of asRNAs and explains their nuclear export.
当 mRNAs 在核内被转录和加工后,它们被运送到细胞质中进行翻译。这种输出是由酵母酿酒酵母(人类中的 TAP-p15)中的输出受体异二聚体 Mex67-Mtr2 介导的。有趣的是,许多长非编码 RNA(lncRNA)也离开细胞核,但目前尚不清楚它们为什么会转移到细胞质中。在这里,我们表明反义 RNA(asRNA)通过与它们的正义对应物退火来加速 mRNA 输出,这是通过解旋酶 Dbp2 实现的。与单链 RNA(ssRNA)相比,这些双链 RNA(dsRNA)具有更高的输出受体 Mex67 的结合能力和亲和力,因此在输出中占主导地位。通过这种方式,asRNA 促进基因表达,这对细胞是有益的。当表达程序发生变化时,这一点尤其重要。因此,dsRNA 的降解或其形成的阻止对细胞是有毒的。这种机制阐明了 asRNA 的普遍存在,并解释了它们的核输出。