Links between mRNA splicing, mRNA quality control, and intellectual disability.

• Type of Material: Article
• Authors: Milo Fasken, Emory University; Anita Corbett, Emory University
• Language: English
• Date: 2016
• Publisher: Smart Science & Technology LLC
• Publication Version: Final Published Version
• Copyright Statement: © 2016 The Authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://www.smartscitech.com/index.php/RD/article/view/1448
• Title of Journal or Parent Work: RNA & Disease
• Volume: 3
• Issue: 4
• Grant/Funding Information: This work was supported by NIH R01 grant (GM058728) to AHC.
• Research Categories: Biology, Genetics; Health Sciences, General; Biology, Neuroscience

Abstract

In recent years, the impairment of RNA binding proteins that play key roles in the post-transcriptional regulation of gene expression has been linked to numerous neurological diseases. These RNA binding proteins perform critical mRNA processing steps in the nucleus, including splicing, polyadenylation, and export. In many cases, these RNA binding proteins are ubiquitously expressed raising key questions about why only brain function is impaired. Recently, mutations in the ZC3H14 gene, encoding an evolutionarily conserved, polyadenosine RNA binding protein, have been linked to a nonsyndromic form of autosomal recessive intellectual disability. Thus far, research on ZC3H14 and its Nab2 orthologs in budding yeast and Drosophila reveals that ZC3H14/Nab2 is important for mRNA processing and neuronal patterning. Two recent studies now provide evidence that ZC3H14/Nab2 may function in the quality control of mRNA splicing and export and could help to explain the molecular defects that cause neuronal dysfunction and lead to an inherited form of intellectual disability. These studies on ZC3H14/Nab2 reveal new clues to the puzzle of why loss of the ubiquitously expressed ZC3H14 protein specifically affects neurons.