Department of Medicine; RNA Therapeutics Institute
Genetic Phenomena | Molecular and Cellular Neuroscience | Nervous System Diseases
The huntingtin gene has two mRNA isoforms that differ in their 3' UTR length. The relationship of these isoforms with Huntington's disease is not established. We provide evidence that the abundance of huntingtin 3' UTR isoforms differs between patient and control neural stem cells, fibroblasts, motor cortex, and cerebellum. Huntingtin 3' UTR isoforms, including a mid-3' UTR isoform, have different localizations, half-lives, polyA tail lengths, microRNA sites, and RNA-binding protein sites. Isoform shifts in Huntington's disease motor cortex are not limited to huntingtin; 11% of alternatively polyadenylated genes change the abundance of their 3' UTR isoforms. Altered expression of RNA-binding proteins may be associated with aberrant isoform abundance; knockdown of the RNA-binding protein CNOT6 in control fibroblasts leads to huntingtin isoform differences similar to those in disease fibroblasts. These findings demonstrate that mRNA 3' UTR isoform changes are a feature of molecular pathology in the Huntington's disease brain.
Huntington’s disease, 3′ UTR isoforms, alternative polyadenylation, huntingtin, polyA site sequencing
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Copyright 2017 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
Cell Rep. 2017 Sep 26;20(13):3057-3070. doi: 10.1016/j.celrep.2017.09.009. Link to article on publisher's site
Romo LS, Ashar-Patel A, Pfister EL, Aronin N. (2017). Alterations in mRNA 3' UTR Isoform Abundance Accompany Gene Expression Changes in Human Huntington's Disease Brains. Open Access Publications by UMMS Authors. https://doi.org/10.1016/j.celrep.2017.09.009. Retrieved from https://escholarship.umassmed.edu/oapubs/3252
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