RNA-binding proteins balance brain function in health and disease.

Posttranscriptional gene expression including splicing, RNA transport, translation and RNA decay provides an important regulatory layer in many if not all molecular pathways. Research in the last decades has positioned RNA-binding proteins (RBPs) right into the center of posttranscriptional gene regulation. We therefore propose interdependent networks of RBPs to regulate complex pathways within the central nervous system (CNS). These are involved in multiple aspects of neuronal formation and functioning including higher cognition. Therefore, it is not sufficient to unravel the individual contribution of a single RBP and its consequences, but rather to study and understand the tight interplay between different RBPs. In this review, we will summarize recent findings in the field of RBP biology in the CNS and discuss the complex interplay between different RBPs. Second, we will emphasize the underlying dynamics within an RBP network and how this might regulate key processes such as neurogenesis, synaptic transmission and synaptic plasticity. Importantly, we envision that dysfunction of specific RBPs could lead to the perturbation within the RBP network. This would have direct and indirect (compensatory) effects in mRNA binding and translational control leading to global changes in cellular expression programs in general and in synaptic plasticity in particular. Therefore, we will focus on RBP dysfunction and how this might cause neuropsychiatric and neurodegenerative disorders. Based on recent findings, we propose that alterations in the entire regulatory RBP network might account for phenotypic dysfunctions observed in complex diseases including neurodegeneration, epilepsy and autism spectrum disorders.