Various sayings equate going fast with going alone. But none of them apply to the gene expression journey described by a research team from the University of Göttingen. The team, led by Heike Krebber, Dr. rer. nat., reported that double-stranded RNA (dsRNA)—that is, antisense RNA (asRNA) annealed to messenger RNA (mRNA)—is preferentially exported from the nucleus to the cytoplasm, boosting gene expression. Essentially, during a crucial part of the gene expression journey, protein-encoding mRNA can go fast by going together…with noncoding antisense RNA.
Details recently appeared in Nature, in an article titled, “dsRNA formation leads to preferential nuclear export and gene expression.” The article’s authors wrote that asRNAs accelerate mRNA export by annealing with their sense counterparts and forming dsDNAs through the helicase Dbp2. The authors added that these dsRNAs dominate export compared with single-stranded RNAs (ssRNAs) because they have a “higher capacity and affinity for the export receptor Mex67.”
It was already known that mRNAs use multiple molecules of yeast heterodimer Mex67–Mtr2 (or human TAP–p15) for export. In the current study, Krebber and colleagues described how they carried out electrophoretic mobility shift assays to show that Mex67–Mtr2 binds “preferentially and more extensively” to dsRNA, explaining its preference in export.
“Our findings reveal a new layer of regulated gene expression,” the scientists concluded. “This mechanism is particularly important for effective cellular adaptation and adds preferential export as a new layer of regulated gene expression. Furthermore, it could also explain how pervasive transcription controls gene expression, and why so many asRNAs are generated and travel into the cytoplasm.”
The function of noncoding RNA in the cell has long been a mystery to researchers. Unlike coding RNA, noncoding RNA does not produce proteins—yet it exists in large quantities.
“It seemed unbelievable to me that a cell would produce RNAs without a purpose,” said Krebber, who is a professor of molecular genetics at Göttingen University’s Institute of Microbiology and Genetics. “This is contrary to nature.”
The ability of asRNA to boost gene expression is necessary for the cell in many situations, for example, when the cell is confronted with harmful environmental conditions or stress. The uncovering of this gene expression mechanism represents the continuation of the Krebber team’s earlier research, also published in Nature, which showed that mRNAs activated under stress are no longer subject to quality control.
The new research findings about asRNAs solve the longstanding question of why the cell sometimes produces large quantities of asRNA. “In biology, this is particularly striking because the cell expends a lot of energy on asRNA production,” Krebber observed. The mechanism that has now been discovered explains how cells can react abruptly to external influences to produce the necessary proteins immediately and in large quantities in order to adapt to environmental conditions or, for example, to enter a certain stage of development. “This new understanding,” Krebber declared, “brings asRNAs into the focus of the question of how diseases develop and how they can be combated.”
