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Summary: Physical exercise stimulates adult hippocampal neurogenesis and is considered a relevant strategy for preventing age-related cognitive decline in humans. The underlying mechanisms remains controversial. Here, we show that exercise increases proliferation of neural precursor cells (NPCs) of the mouse dentate gyrus (DG) via downregulation of microRNA 135a-5p (miR-135a). MiR-135a inhibition stimulates NPC proliferation leading to increased neurogenesis, but not astrogliogenesis, in DG of resting mice, and intriguingly it re-activates NPC proliferation in aged mice. We identify 17 proteins (11 putative targets) modulated by miR-135 in NPCs. Of note, inositol 1,4,5-trisphosphate (IP3) receptor 1 and inositol polyphosphate-4-phosphatase type I are among the modulated proteins, suggesting that IP3 signaling may act downstream miR-135. miR-135 is the first noncoding RNA essential modulator of the brain's response to physical exercise. Prospectively, the miR-135-IP3 axis might represent a novel target of therapeutic intervention to prevent pathological brain aging. : Pons-Espinal, Gasperini, and colleagues report that running induces NPC proliferation and neurogenesis via downregulation of miR-135a-5p in the mouse hippocampus. Remarkably, downregulation of miR-135a stimulates proliferation in the hippocampus of aged mice. ITPR1 and INPP4A, involved in IP3 signaling, are modulated by miR-135 in NPCs. Prospectively, therapeutic exploitation of the miR-135-IP3 axis might represent a novel intervention strategy for successful aging. Keywords: adult neurogenesis, running, aging, miR-135a, inositol 1,4,5-trisphosphate (IP3) pathway, ITPR1, INPP4A

Several lncRNAs are regulated by TGF-β. Here the authors report that an intergenic lncRNA —EPR— is a component of the TGF-β signaling pathway and controls epithelial cell proliferation by altering transcription and mRNA decay of Cdkn1a. EPR overexpression restrains tumor growth of orthotopically transplanted mice.

Via the target-directed miRNA degradation process, RNAs can induce degradation of miRNAs by binding with extensive complementarity. Here, the authors show Serpine1 mRNA as one such RNA that can control the levels of the endogenous miRNA miR-30b/c-5p by modulating miRNA degradation.