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dsRNA formation leads to preferential nuclear export and gene expression

Ivo Coban1, Jan-Philipp Lamping1, Anna Greta Hirsch1

  • 1Abteilung für Molekulare Genetik, Institut für Mikrobiologie und Genetik, Göttinger Zentrum für Molekulare Biowissenschaften (GZMB), Georg-August Universität Göttingen, Göttingen, Germany.

Nature
|June 19, 2024
PubMed

Insights

Antisense RNAs (asRNAs) enhance gene expression by forming double-stranded RNAs (dsRNAs) with messenger RNAs (mRNAs). These dsRNAs are preferentially exported from the nucleus, boosting protein production.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Messenger RNAs (mRNAs) are exported from the nucleus to the cytoplasm for translation, mediated by export receptors like Mex67-Mtr2.
  • The function of long non-coding RNAs (lncRNAs) in nuclear export remains largely unknown.
  • Antisense RNAs (asRNAs) are a class of non-coding RNAs with emerging roles in gene regulation.

Purpose of the Study:

  • To investigate the role of asRNAs in nuclear export and gene expression.
  • To elucidate the mechanism by which asRNAs influence mRNA export.
  • To understand the cellular significance of asRNA-mediated nuclear export.

Main Methods:

  • Investigated the interaction between asRNAs, sense RNAs, and the helicase Dbp2 in Saccharomyces cerevisiae.
  • Analyzed the export efficiency of single-stranded RNAs (ssRNAs) versus double-stranded RNAs (dsRNAs) mediated by the Mex67 export receptor.
  • Assessed the impact of dsRNA degradation and formation prevention on cell viability.

Main Results:

  • asRNAs anneal with their sense counterparts, forming dsRNAs that are preferentially exported from the nucleus.
  • These dsRNAs exhibit higher affinity and capacity for the Mex67 export receptor compared to ssRNAs.
  • The formation of dsRNA by asRNAs accelerates mRNA export and boosts gene expression.
  • Interference with dsRNA formation or degradation is toxic to cells, highlighting its essential role.

Conclusions:

  • asRNAs play a crucial role in enhancing gene expression by facilitating mRNA nuclear export.
  • The formation of dsRNA is a key mechanism by which asRNAs promote cellular function.
  • This mechanism explains the widespread occurrence and nuclear export of asRNAs, particularly during changing expression programs.

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