期刊
SCHIZOPHRENIA BULLETIN
卷 40, 期 2, 页码 399-409出版社
OXFORD UNIV PRESS
DOI: 10.1093/schbul/sbs198
关键词
aging; schizophrenia; miRNA; neurodevelopment; prefrontal cortex
类别
资金
- New South Wales Ministry of Health
- Macquarie Group Foundation
- National Health and Medical Research Council of Australia
- Schizophrenia Research Institute
- National Institute of Alcohol Abuse and Alcoholism [R24AA012725]
- National Health and Medical Research Council [631057]
- National Alliance for Research on Schizophrenia and DepressionYoung Investigator Award
- Hunter Medical Research Institute
- M.C. Ainsworth Research Fellowship in Epigenetics
- National Health and Medical Research Council of Australia [1021970]
- University of New South Wales
- Neuroscience Research Australia
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 over-represented 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.
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