Experimental Cerebral Ischemia Affects the Expression of Circular RNA Genes of Metabotropic Glutamate Receptors mGluR(3) and mGluR(5) in Rat Brain
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
Authors: Filippenkov, I. B.; Stavchansky, V. V.; Denisova, A. E.; Ivanova, K. A.; Limborska, S. A.; Dergunova, L. V.
Abstract
Circular RNAs (circRNAs) are a new RNA type that show predominantly brain-specific expression pattern in mammals. Their individual representatives, acting as competitive endogenous RNAs, can bind microRNAs and contribute to the protection of functional transcripts. In the model of transient cerebral ischemia in rats, we studied the expression of mGluR(3) and mGluR(5) glutamate metabotropic receptor genes (Grm3 and Grm5). These genes are important participants in the metabolic pathways associated with neurosignaling. In the present study, we found that the rat Grm3 and Grm5 genes, in addition to mRNA, encode circRNAs, which are conserved in humans and rodents. In subcortical brain structures of rats containing a lesion focus, the level of these circRNAs is more stable than that of the corresponding mRNA. Using STarMirDB database analysis, the distribution of the microRNA binding sites along the mRNA molecules of human GRM3 and GRM5 genes which are homologous to the corresponding rat genes was elucidated. It has been revealed that sufficiently large number of binding sites is located within exons, which are also part of conservative circRNAs. The results may indicate the functional role of the circRNAs of the investigated genes as competitive endogenous RNAs in the response of brain cells to ischemia.
Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes
MOLECULAR PSYCHIATRY
Authors: Elia, J.; Gai, X.; Xie, H. M.; Perin, J. C.; Geiger, E.; Glessner, J. T.; D'arcy, M.; deBerardinis, R.; Frackelton, E.; Kim, C.; Lantieri, F.; Muganga, B. M.; Wang, L.; Takeda, T.; Rappaport, E. F.; Grant, S. F. A.; Berrettini, W.; Devoto, M.; Shaikh, T. H.; Hakonarson, H.; White, P. S.
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients and their parents that were not detected in 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, were found in the ADHD cohort relative to controls, the inherited rare CNV-associated gene set was significantly enriched for genes reported as candidates in studies of autism, schizophrenia and Tourette syndrome, including A2BP1, AUTS2, CNTNAP2 and IMMP2L. The ADHD CNV gene set was also significantly enriched for genes known to be important for psychological and neurological functions, including learning, behavior, synaptic transmission and central nervous system development. Four independent deletions were located within the protein tyrosine phosphatase gene, PTPRD, recently implicated as a candidate gene for restless legs syndrome, which frequently presents with ADHD. A deletion within the glutamate receptor gene, GRM5, was found in an affected parent and all three affected offspring whose ADHD phenotypes closely resembled those of the GRM5 null mouse. Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD. Molecular Psychiatry (2010) 15, 637-646; doi: 10.1038/mp.2009.57; published online 23 June 2009
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