Role of RNA Methylation and Non-Coding RNAs in Pathobiology of Autism Spectrum Disorders
Vichithra Rasangi Batuwita Liyanage
Issue:
Volume 2, Issue 4, July 2016
Pages:
24-33
Received:
6 June 2016
Accepted:
12 July 2016
Published:
27 August 2016
DOI:
10.11648/j.bs.20160204.11
Downloads:
Views:
Abstract: Autism Spectrum Disorders (ASD) are a multifaceted set of neurodevelopmental disorders caused by diverse genetic, epigenetic and environmental factors. Epigenetic mechanisms such as DNA methylation regulate gene expression without changing the genomic DNA sequence, but changing how genomic information is interpreted. The identification of RNA molecules such as non-coding RNAs and its modifications such as RNA methylation as separate functional entities caused a paradigm shift in the epigenetic field. Recent advances have demonstrated that epigenetic mechanisms involving RNA molecules could be immensely contributing to the complex ASD pathobiology. Indirect evidence suggests that methylation of mRNA could be functioning as a regulatory switch in maintaining a balance between mRNA turnover and protein synthesis in autistic patients. Moreover, many studies provide supporting evidence that alterations to ‘the methylation cycle’, which extend to the methionine-homocysteine pathway, folate cycle, and the redox-homeostasis pathway could underwrite the reduced methylation capacity in ASD. This, in turn, may reduce the RNA methylation status in autistic patients. While implications of RNA methylation in ASD is intriguing, the direct role of RNA methylation in ASD pathogenesis is yet to be explored in depth. In contrast, the functional aspects of non-coding RNAs – both microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) – in ASD have been investigated. MiRNAs found in the autistic brain, blood, saliva or lymphoblast cell lines have shown differential expression as well as deregulation of their target genes. These miRNAs and target genes are associated with synaptic processes, synaptic plasticity, memory, neuronal morphology as well as many cell signaling pathways which could be contributing to the pathobiology of ASD. Similarly, many lncRNAs are differentially expressed in autistic patients and are involved in the deregulation of neuronal connectivity, synaptic functions, and imprinting. Interestingly, some of these lncRNAs are associated with increased risk of ASD. Collectively, epigenetic mechanisms provide codes for maintenance of proper cellular functions. When these epigenetic mechanisms are miscoded, the altered expression of genes, cellular processes and functions contribute towards the pathogenesis of ASD. Therefore, understanding these miscoded RNA epigenetic mechanisms will hold promise for future therapeutic developments for ASD.
Abstract: Autism Spectrum Disorders (ASD) are a multifaceted set of neurodevelopmental disorders caused by diverse genetic, epigenetic and environmental factors. Epigenetic mechanisms such as DNA methylation regulate gene expression without changing the genomic DNA sequence, but changing how genomic information is interpreted. The identification of RNA molec...
Show More
