Neurons and glia are highly polarized cells that achieve their specialized functions largely due to their high complexity of regulating gene expression. In particular, these cells critically contribute to every step in the regulation of the mRNA life cycle in a unique manner. For example, the brain has the highest levels of alternative splicing and RNA editing. Many of the alternatively spliced isoforms of a given protein produced in brain are required for neuronal development, synaptic transmission and plasticity. However, the effects of RNA processing on the functions of resulting protein isoforms are still poorly understood. Further layers of regulation are added by control of mRNA transport, translation or degradation. Most importantly, these regulatory processes can take place within neuronal axons and dendrites, due to the unique ability of neurons to transport mRNAs far from the cell body. Regulation of mRNA translation in specific neuronal compartments is crucial for neuronal functions that take place far from cell body, such as axon guidance and synaptic plasticity.
The mRNA life cycle is orchestrated by a complex interplay of RNA binding proteins (RBPs) and non-coding RNAs, which can interact at many different positions on pre-mRNAs and mRNAs, and often form larger particles that mediate mRNA transport or degradation. Mutations in several RBPs, toxic RNA repeats, or other defects in post-transcriptional regulation contribute to a variety of neurologic diseases. In most cases, the mechanisms leading to the neurologic defects are poorly understood. To understand the full complexity of post-transcriptional regulation, and how it can go awry in the brain, new experimental and computational approaches are being developed. In this volume, we have asked leaders in the field to overview the literature of published research, present results of their current research, and provide their thoughts on the new developments and future directions of the field.
Neurons and glia are highly polarized cells that achieve their specialized functions largely due to their high complexity of regulating gene expression. In particular, these cells critically contribute to every step in the regulation of the mRNA life cycle in a unique manner. For example, the brain has the highest levels of alternative splicing and RNA editing. Many of the alternatively spliced isoforms of a given protein produced in brain are required for neuronal development, synaptic transmission and plasticity. However, the effects of RNA processing on the functions of resulting protein isoforms are still poorly understood. Further layers of regulation are added by control of mRNA transport, translation or degradation. Most importantly, these regulatory processes can take place within neuronal axons and dendrites, due to the unique ability of neurons to transport mRNAs far from the cell body. Regulation of mRNA translation in specific neuronal compartments is crucial for neuronal functions that take place far from cell body, such as axon guidance and synaptic plasticity.
The mRNA life cycle is orchestrated by a complex interplay of RNA binding proteins (RBPs) and non-coding RNAs, which can interact at many different positions on pre-mRNAs and mRNAs, and often form larger particles that mediate mRNA transport or degradation. Mutations in several RBPs, toxic RNA repeats, or other defects in post-transcriptional regulation contribute to a variety of neurologic diseases. In most cases, the mechanisms leading to the neurologic defects are poorly understood. To understand the full complexity of post-transcriptional regulation, and how it can go awry in the brain, new experimental and computational approaches are being developed. In this volume, we have asked leaders in the field to overview the literature of published research, present results of their current research, and provide their thoughts on the new developments and future directions of the field.
