UMMS Affiliation
Program in Molecular Medicine
Publication Date
2021-09-10
Document Type
Article
Disciplines
Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Nervous System Diseases | Neuroscience and Neurobiology | Nucleic Acids, Nucleotides, and Nucleosides | Psychiatry | Psychiatry and Psychology
Abstract
Fragile X Syndrome is a neuro-developmental disorder caused by the silencing of the FMR1 gene, resulting in the loss of its protein product, FMRP. FMRP binds mRNA and represses general translation in the brain. Transcriptome analysis of the Fmr1-deficient mouse hippocampus reveals widespread dysregulation of alternative splicing of pre-mRNAs. Many of these aberrant splicing changes coincide with those found in post-mortem brain tissue from individuals with autism spectrum disorders (ASDs) as well as in mouse models of intellectual disability such as PTEN hamartoma syndrome (PHTS) and Rett Syndrome (RTT). These splicing changes could result from chromatin modifications (e.g., in FXS, RTT) and/or splicing factor alterations (e.g., PTEN, autism). Based on the identities of the RNAs that are mis-spliced in these disorders, it may be that they are at least partly responsible for some shared pathophysiological conditions. The convergence of splicing aberrations among these autism spectrum disorders might be crucial to understanding their underlying cognitive impairments.
Keywords
Fragile X syndrome, alternative splicing, autism, gene regulation, intellectual disability
Rights and Permissions
Copyright © 2021 Shah and Richter. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
DOI of Published Version
10.3389/fpsyt.2021.715346
Source
Shah S, Richter JD. Do Fragile X Syndrome and Other Intellectual Disorders Converge at Aberrant Pre-mRNA Splicing? Front Psychiatry. 2021 Sep 10;12:715346. doi: 10.3389/fpsyt.2021.715346. PMID: 34566717; PMCID: PMC8460907. Link to article on publisher's site
Journal/Book/Conference Title
Frontiers in psychiatry
Related Resources
PubMed ID
34566717
Repository Citation
Shah S, Richter JD. (2021). Do Fragile X Syndrome and Other Intellectual Disorders Converge at Aberrant Pre-mRNA Splicing. Open Access Publications by UMass Chan Authors. https://doi.org/10.3389/fpsyt.2021.715346. Retrieved from https://escholarship.umassmed.edu/oapubs/4943
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons, Nervous System Diseases Commons, Neuroscience and Neurobiology Commons, Nucleic Acids, Nucleotides, and Nucleosides Commons, Psychiatry Commons, Psychiatry and Psychology Commons