A new study by researchers at The George Washington University School of Medicine and Health Sciences’ Department of Biochemistry and Molecular Biology highlights a mechanism for significant disruption of gene activity in autism that may be reversible. Published in the journal Genome Medicine on April 7, the study focuses on the differential expression of microRNA and addresses the issue of higher level regulation of gene expression in autism.
MicroRNA are recently discovered snippets of RNA (ribonucleic acid), each of which can inhibit the expression (and thus activity) of hundreds to more than a thousand genes. The effects of microRNA are also reversible by treatment with complementary “anti-sense” RNA.
Valerie Hu, Ph.D., professor of Biochemistry and Molecular Biology, with a GW graduate student and collaborators at the National Institute of Mental Health, identified changes in the profile of microRNAs between identical twins and sibling pairs, discordant for diagnosis of autism. They discovered that, despite using cells derived originally from blood, brain-specific and brain-related microRNAs were found to be differentially expressed in the autistic samples, and that these microRNAs could potentially regulate genes that control many processes known to be disrupted in autism. For example, differentially expressed microRNAs were found to regulate genes highly involved in neurological functions and disorders in addition to genes involved in gastrointestinal diseases, circadian rhythm signaling, and steroid hormone metabolism.
The study further shows that by treating the cells with “anti-sense” RNA antagonists (inhibitors) to specific microRNA or by employing mimics of a particular microRNA, one can reverse the pattern of expression of a given target gene regulated by that microRNA.
This study, titled “Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders by microRNA expression profiling of lymphoblastoid cell lines” was highlighted as an “Editor’s pick” in Genome Medicine. It is available online at: http://genomemedicine.com/content/2/4/23.
When paired with another recently published study regarding “DNA tagging” by methylation, Dr. Hu’s research illustrates two different “epigenetic” mechanisms controlling gene activity in autism that lie beyond genetic mutations. While methylation inhibits gene expression at the level of DNA, microRNA inhibits at the level of RNA. By integrating both DNA methylation and microRNA expression studies with gene expression data, Dr. Hu and her team are applying a systems biology approach to understanding this complex disorder.
“It is becoming increasingly clear that many factors, genetic as well as epigenetic, contribute to the manifestation of autism spectrum disorders,” said Dr. Hu. “Epigenetic factors are particularly interesting as they provide potential mechanisms for introducing environmental effects into this complex disorder.”
About The George Washington University Medical CenterThe George Washington University Medical Center is an internationally recognized interdisciplinary academic health center that has consistently provided high-quality medical care in the Washington, D.C. metropolitan area since 1824. The Medical Center comprises the School of Medicine and Health Sciences, the 11th oldest medical school in the country; the School of Public Health and Health Services, the only such school in the nation’s capital; GW Hospital, jointly owned and operated by a partnership between The George Washington University and a subsidiary of Universal Health Services, Inc.; and The GW Medical Faculty Associates, an independent medical practice with nearly 350 physicians in 42 clinical specialties. For more information on GWUMC, visit www.gwumc.edu.