Press Page Elena Conti

mRNA Quality Control inside the Cell

In eukaryotic cells, there is a continuous exchange of information between the nucleus and the cytoplasm. To ensure that no errors occur during these complex processes, the cell has a highly sophisticated quality control system at its disposal. The scientists in the research department led by Elena Conti investigate how information exchange and how error detection and elimination work inside the cell.

Ribonucleic acids (RNAs) serve as important messengers between the nucleus of a cell and its cytoplasm: messenger RNAs (mRNAs) contain the information of how new proteins will be built. Errors in these protein construction plans can lead to severe problems and are in some cases the cause of serious diseases. Cells possess a sophisticated quality control system to counteract such errors. In order to understand how this surveillance system works, the scientists must eventually visualize the atomic structure of the protein and RNA complexes involved.

Shiny crystals with inner beauty

To obtain structural information, the scientists first form crystals of the molecules under study and shine X-rays onto them. The diffraction patterns that emerge are used to compute maps that contain information on the distribution of the electrons in the molecule. This is a molecular blueprint, which corresponds to the arrangement and sequel of atoms that are specific of each protein and RNA. The internal order of the crystals thus allows scientists to look at the structure of the molecules they contain.

Errors are eliminated

In this way, the scientists have been able to elucidate the crystal structure of the exon junction complex (EJC), a protein complex that plays a crucial role in the quality control of human cells. The EJC is loaded onto the mRNA in the nucleus and is then transferred to the cytoplasm. Here, the EJC relays positional information to the translation machinery, allowing the cell to detect sites of errors in the mRNA where protein synthesis would end prematurely. The scientists have uncovered how the EJC grips tightly on the mRNA and recruits the first protein of the quality control detection system. Elena Conti and her team are now concentrating on finding out the steps leading to the destruction of the erroneous messenger RNAs.


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Elena Conti and F. Ulrich Hartl

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The image shows the cryoEM reconstruction from the nuclease complex with RBBP6, part of the protein machinery that cleaves mRNA.

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