Journal
ACTA NEUROPATHOLOGICA
Volume 137, Issue 4, Pages 535-555Publisher
SPRINGER
DOI: 10.1007/s00401-019-01971-8
Keywords
mRNA translation; RNA-binding proteins; Neurodegenerative diseases; Brain tumors; eEF2 kinase; Translation control
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Funding
- Canadian Cancer Society Research Institute (CCSRI) Impact Grant [703205]
- CIHR Foundation Grant [FDN-143280]
- Harry and Florence Dennison Fellowship in Medical Research
- 4 Year Fellowship
- Killam Doctoral Scholarship from the University of British Columbia, BC, Canada
- European Union [754513]
- Lundbeckfonden, Denmark [R250-2017-1131]
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Messenger RNA (mRNA) translation is the terminal step in protein synthesis, providing a crucial regulatory checkpoint for this process. Translational control allows specific cell types to respond to rapid changes in the microenvironment or to serve specific functions. For example, neurons use mRNA transport to achieve local protein synthesis at significant distances from the nucleus, the site of RNA transcription. Altered expression or functions of the various components of the translational machinery have been linked to several pathologies in the central nervous system. In this review, we provide a brief overview of the basic principles of mRNA translation, and discuss alterations of this process relevant to CNS disease conditions, with a focus on brain tumors and chronic neurological conditions. Finally, synthesizing this knowledge, we discuss the opportunities to exploit the biology of altered mRNA translation for novel therapies in brain disorders, as well as how studying these alterations can shed new light on disease mechanisms.
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