Institut de biologie moléculaire des plantes » RNA-Based Gene Silencing Across Eukaryotes: An Epitranscriptomic and YTH proteins Perspective

Dr André VERDEL, Institut pour l'Avancée des Biosciences, Université Grenoble Alpes, France, invité par C. Bousquet-Antonelli

YTH proteins are RNA-binding proteins (RBPs) that contain a highly conserved YTH domain, which specifically recognizes N6-methyladenosine (m⁶A), the most abundant internal modification of RNA. Through this interaction, YTH proteins mediate key biological processes such as chromatin modification, RNA maturation, degradation, and export. These YTH-dependent functions can effectively silence gene expression and are essential for regulating cell differentiation, early development, and cellular responses to stress. Moreover, dysregulation of YTH protein function is associated with a variety of pathological conditions.

Early biophysical and structural studies of the YTH domain’s ability to bind m⁶A led to the widespread assumption that this epitranscriptomic interaction is autonomous—that is, the YTH domain alone is sufficient for m⁶A recognition, and that its binding activity is not subject to regulation.

However, I will present two recent studies from our group that provide strong evidence that YTH–RNA interactions are, in fact, regulated in yeast, plants, and humans. Our findings indicate that YTH-mediated recognition of m⁶A is subject to control, potentially serving as a major mechanism to fine-tune both the sequence specificity and binding affinity of these proteins—an important feature that remained undetected and that may be widespread among eukaryotes.

20juin2025

RNA-Based Gene Silencing Across Eukaryotes: An Epitranscriptomic and YTH proteins Perspective

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