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Nuclear Export01:42

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The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of  2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
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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.

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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.

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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.