Taken together with recently published research regarding “DNA tagging” by methylation, they say their new study in Genome medicine 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.
MicroRNA are snippets of RNA, each of which can inhibit the expression of hundreds to more than a thousand genes. The effects of microRNA are also reversible by treatment with complementary “anti-sense” RNA.
The George Washington University team 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 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.
“It is becoming increasingly clear that many factors, genetic as well as epigenetic, contribute to the manifestation of autism spectrum disorders,” said Valerie Hu, from the University's School of Medicine. “Epigenetic factors are particularly interesting as they provide potential mechanisms for introducing environmental effects into this complex disorder.”
Citation: Sarachana et al., 'Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders by microRNA expression profiling of lymphoblastoid cell lines', Genome Medicine, April 2010, 2(23); doi:10.1186/gm144
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