title: Maturation of the human dorsolateral prefrontal cortex coincides with a dynamic shift in microRNA expression.
abstract: MicroRNA are small RNAs that provide specificity for the RNA induced silencing complex, which forms the basis of an exquisite combinatorial system for posttranscriptional regulation. This system, essential for complex metazoans, is exemplified in the development of the cerebral cortex. To explore the complexity of human cortical miRNA expression in detail, we analyzed RNA from postmortem prefrontal cortex from 97 subjects aged 2 months to 78 years using miRNA microarray. Global miRNA expression was highest in the early years before declining significantly after adolescence (n = 140 decreased, n = 32 increased). Late adolescence was also marked by an inflection point between miRNA on an upward trajectory vs the majority going down. Functional annotation of target genes displaying inverse mRNA expression patterns in the same tissue were overrepresented in neurodevelopmentally significant pathways including neurological disease (most significantly schizophrenia), nervous system development, and cell-to-cell signaling. As mature miRNA expression is largely posttranscriptionally regulated, miRNA biogenesis gene expression was also examined. Dicer and Exportin-5 displayed significant associations with age; however, neither correlated with global miRNA expression across the lifespan. This investigation of cortical miRNA expression provides a framework for understanding the complex posttranscriptional regulatory environment during development and aging that may form a substrate for changes observed in neurodevelopmental disorders.
authors: To whom correspondence should be addressed; School of Biomedical Sciences & Pharmacy, The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia; tel: +61-2-4921-8670, fax: +61-2-4921-7903, e-mail: murray.cairns@newcastle.edu.au.
authors: Natalie J
authors: NJ
authors: Beveridge
authors: Danielle M
authors: DM
authors: Santarelli
authors: Xi
authors: X
authors: Wang
authors: Paul A
authors: PA
authors: Tooney
authors: Maree J
authors: MJ
authors: Webster
authors: Cynthia S
authors: CS
authors: Weickert
authors: Murray J
authors: MJ
authors: Cairns
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D053487:DEAD-box RNA Helicases / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006803:Human Development / Q000502:physiology*; D006801:Humans; D007223:Infant; D028884:Karyopherins / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D043244:Ribonuclease III / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*; D014015:Tissue Banks; D055815:Young Adult
chemical_list: D028884:Karyopherins; D035683:MicroRNAs; C446511:XPO5 protein, human; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: aging; ment; miRNA; neurodevelop‐; prefrontal cortex; schizophrenia
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