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Researchers identify an enzyme essential for development

An international collaboration to which Marc Graille's team, CNRS Research Director at the Laboratory of Structural Biology of the Cell, is contributing has identified an important enzyme that acts on the ribosome and allows normal development of the animal brain and normal walking in Drosophila.

Representation of the three-dimensional structure of the human METTL5-TRMT112 complex and the phenotype observed in the fly following inactivation of the METTL5 gene.

In living organisms, the translation of genetic material into proteins is carried out by the ribosome. This nano-machine is manufactured by a very complex and highly coordinated process involving more than 200 assembly proteins and many RNAs that do not encode for proteins.

Understanding the ribosome and how it works is crucial because defects in its structure can be lethal at the embryonic stage or lead to the development of blood diseases or cancers.

The teams of Marc Graille, CNRS Research Director at the Laboratory of Structural Biology of the Cell (BIOC*), Denis Lafontaine (Université Libre de Bruxelles, Belgium) and Jean-Yves Roignant (Institute of Molecular Biology, Mainz, Germany & University of Lausanne, Switzerland) have combined their skills to unravel an essential role of the methyltransferase protein METTL5 in the addition of a methyl group on a specific base (N6-methyladenine or m6A) within the decoding center, commonly referred to as the ribosome "brain".

These researchers have then inactivated the gene coding for the METTL5 protein in the Drosophila melanogaster fly and observed that flies inactivated for this enzyme had motor problems (disoriented walking, see Figure).

This work highlights the importance of this small chemical grouping in gene expression and animal behaviour and echoes other very recent studies showing that METTL5 inactivated mutations cause intellectual disorders microcephalies and craniofacial abnormalities in humans.

This research has been published in the journals Nucleic Acids Research and EMBO Reports.

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*BIOC: a joint research unit CNRS - École polytechnique