dsRNA formation leads to preferential nuclear export and gene expression

Ivo Coban, Jan-Philipp Lamping, Anna Greta Hirsch, Sarah Wasilewski, Orr Shomroni, Oliver Giesbrecht, Gabriela Salinas and Heike Krebber ()
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Ivo Coban: Georg-August Universität Göttingen
Jan-Philipp Lamping: Georg-August Universität Göttingen
Anna Greta Hirsch: Georg-August Universität Göttingen
Sarah Wasilewski: Georg-August Universität Göttingen
Orr Shomroni: University Medical Center Göttingen
Oliver Giesbrecht: Georg-August Universität Göttingen
Gabriela Salinas: University Medical Center Göttingen
Heike Krebber: Georg-August Universität Göttingen

Nature, 2024, vol. 631, issue 8020, 432-438

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41586-024-07576-w

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