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mRNA quality control mechanism prevents contamination of cells

Researchers from Aarhus University have just disclosed a new quality control mechanism that prevents contamination of cells with aberrant mRNA. This helps us to understand how mRNA quality control can act in a precautionary way to avoid the cellular spreading of toxic molecules.

2012.08.24 | Lisbeth Heilesen

In collaboration with French scientists, PhD student Thomas B. Kallehauge (right) and Professor Torben Heick Jensen shed light on a phenomenon where the export of mRNA is corrupted. The study shows that mRNA retained in nuclear dots is translationally active and that such dots may function as nuclear storage sites for immature mRNA (Photo: Estelle Marchal).

Newly discovered function for dot mRNA

For cells to function, they need to produce a wide range of different proteins. To facilitate this, corresponding mRNAs need to be transcribed from their genes and be exported from the cell nucleus to the cytoplasm, where protein translation occurs. En route to the cytoplasm, the mRNA is packaged with different export factors, which serve to mature the mRNA and make it competent for export.

Curiously, in cells of baker’s yeast (Saccharomyces cerevisiae) that are mutated for certain such mRNA export factors, mRNA accumulates in close proximity to the gene. This accumulated material (affectionately termed dots) was believed to be dead-end products simply awaiting nuclear degradation. However, by using advanced microscopic techniques to enable the detection of single mRNA molecules – in combination with classical molecular biological methods – PhD student Thomas B. Kallehauge has now revealed a hitherto unknown and unexpected fate of dot mRNA.

Dots are beneficial

Surprisingly, Thomas B. Kallehauge was able to show that dot mRNA was functional if enough time was provided to let the mRNA contained in the dot mature and travel to the cytoplasm. In contrast, artificially forcing dot mRNA to the cytoplasm did not yield any protein, but instead triggered a severe growth deficiency.

The results – that have just been published online in the prestigious American journal Molecular Cell – indicate that storage of improperly produced mRNA in nuclear dots is actually beneficial for the cell. Over time, stored mRNA will mature and eventually be exported for cytoplasmic protein production. Physiologically, this may be relevant when cells are subjected to different forms of stresses that affect the efficiency of mRNA production.

 

Future studies

Future efforts will be devoted to exploring the RNA/protein composition of dot mRNA, as well as describing a similar phenomenon that occurs in human cells.

The research project was carried out in Professor Torben Heick Jensen’s laboratory at the Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, Denmark. The centre is funded by the Danish National Research Foundation. Thomas B. Kallehauge carried out part of his research in Edouard Bertrand’s laboratory at the Institute of Molecular Genetics of Montpellier (IGMM) in France, where he spent a period of fifteen months.


Link to the article:

Nuclear Retention Prevents Premature Cytoplasmic Appearance of mRNA

Thomas Beuchert Kallehauge1, 2, Marie-Cécile Robert2, Edouard Bertrand2,  and Torben Heick Jensen1

1 Department of Molecular Biology and Genetics, Centre for mRNP Biogenesis and Metabolism, C.F. Møllers Allé, Building 1130, Aarhus University, 8000 Aarhus C, Denmark
2 Institute de Génétique Moléculaire Montpellier, Unité Mixte de Recherche 5535, CNRS, 34293 Montpellier, France


Further information

Professor Torben Heick Jensen
Director of the Centre for mRNP Biogenesis and Metabolism
Department of Molecular Biology and Genetics, Aarhus University, Denmark
thj@mb.au.dk
- +45 6020 2705 - www.mRNP.dk

Public / media, Department of Molecular Biology and Genetics, mRNP