德国哥廷根大学Heike Krebber研究小组发现，dsRNA的形成导致优先核输出和基因表达。该项研究成果于2024年6月19日在线发表在《自然》杂志上。

研究人员发现反义RNA（asRNA）通过螺旋酶Dbp2与正义RNA退火，从而加速了mRNA的输出。与单链RNA（ssRNA）相比，这些双链RNA（dsRNA）具有更强的输出能力和对输出受体Mex67的亲和力，因此在输出过程中占主导地位。因此，asRNA就能促进基因表达，对细胞有益。当表达程序发生变化时，这一点尤为重要。因此，dsRNA的降解或阻止其形成对细胞来说是有毒的。这一机制揭示了asRNA在细胞中的普遍存在，并解释了其核输出的原因。

据悉，mRNA在细胞核中转录和加工后，会被输出到细胞质中进行翻译。这种输出是由酵母中的输出受体异二聚体Mex67-Mtr2（人类中为TAP-p15）介导的。有趣的是，许多长非编码RNA（lncRNA）也会离开细胞核，但目前还不清楚它们为什么会转移到细胞质。

附：英文原文

Title: dsRNA formation leads to preferential nuclear export and gene expression

Author: Coban, Ivo, Lamping, Jan-Philipp, Hirsch, Anna Greta, Wasilewski, Sarah, Shomroni, Orr, Giesbrecht, Oliver, Salinas, Gabriela, Krebber, Heike

Issue&Volume: 2024-06-19

Abstract: 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)1,2. Interestingly, many long non-coding RNAs (lncRNAs) also leave the nucleus but it is currently unclear why they move to the cytoplasm3. 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.

DOI: 10.1038/s41586-024-07576-w

Source: https://www.nature.com/articles/s41586-024-07576-w