Targeting an RNA-Binding Protein to Fight Aging

A study published in Molecular Cell examined the connection between aging and RNA-binding proteins (RBPs), which bind mRNA molecules and regulate what happens to them after gene transcription, reports ScienceDaily . The researchers initially screened aged animals to identify any RBPs that change with age, and found a specific protein, Pumilio2 (PUM2), exhibited high induction. PUM2 binds mRNA molecules containing specific recognition sites, then represses the translation of the target mRNAs into proteins. The team identified a new mRNA site that PUM2 binds: the mRNA encodes for Mitochondrial Fission Factor (MFF), regulating the process by which mitochondria break up into smaller mitochondria. High MFF levels also enable the clearance of fragmented, dysfunctional mitochondria. The PUM2/MFF axis is "dysregulated" with age, and the removal of PUM2 from the muscles of old mice can reverse MFF level reduction and the accumulation of bigger and unhealthy organelles in tissues. "Reducing PUM2 levels, we obtained more MFF protein and increased mitochondrial fragmentation and mitophagy," says the Ecole Polytechnique Fédérale de Lausanne's Davide D'Amico. "Notably, the consequence was a significant improvement of the mitochondrial function of the old animals."