Global Exploration of RNA-Binding Proteins in Exercise-Induced Adult Hippocampal Neurogenesis: A Transcriptome Meta-analysis and Computational Study

Abstract

Voluntary physical exercise is a robust enhancer of adult hippocampal neurogenesis (AHN). A complete understanding of the molecular regulation of AHN is important in order to exploit the benefits of the process toward therapeutic approaches. Several factors such as epigenetic modifiers, non-coding RNAs, and transcription factors have been reported to regulate AHN. However, there is a limited understanding of the impact of RNA-binding proteins (RBPs) on exercise-mediated AHN, in spite of their well-documented significance in embryonic neurogenesis. The present study is the first global analysis to catalog the potential RBPs influencing exercise-mediated AHN. Here, a transcriptome meta-analysis was conducted to study exercise-mediated gene expression modulation in hippocampi of adult mice. Next, potential RBPs influencing transcriptome-wide expression changes via untranslated regions (UTRs) were identified. Among other RBPs, MATR3, Musashi, TIA1, and FXR2 (known critical modulators of neurogenesis) were found to potentially regulate gene expression patterns. Subsequently, binding sites of known neurogenesis-regulating RBPs were identified in the UTRs of AHN-associated genes modulated by exercise. Finally, a number of RBPs including RBFOX1, RBFOX3, and QKI (known regulators of neurogenesis) were found to be highly expressed in mouse hippocampal formation and also potentially interact with other RBPs, suggesting their combinatorial functioning in exercise-induced AHN. Thus, the present meta-analysis-based computational study identified several RBPs potentially important in exercise-induced AHN, which could form a foundation for further experiments to unravel RBP-mediated regulation of AHN.

Keywords: Adult hippocampal neurogenesis; Exercise; Meta-analysis; RNA-binding proteins.