MicroRNA-9 and MicroRNA-326 Regulate Human Dopamine D2 Receptor Expression, and the MicroRNA-mediated Expression Regulation Is Altered by a Genetic Variant

Shi, Sandra; Leites, Catherine; He, Deli; Schwartz, D.; Moy, Winton; Shi, Jianxin; Duan, Jubao

doi:10.1074/jbc.m113.535203

Cited by 52 publications

(43 citation statements)

References 82 publications

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“…The dopamine receptor D2 (DRD2) gene, a downstream target of miR-9, is also implicated in the pathophysiology of schizophrenia. The SNP rs1801028 (Cys311Ser) in DRD2 is linked to schizophrenia in a metaanalysis (Glatt et al, 2003;Shi et al, 2014). An inverse correlation in the expression of DRD2 and miR-9 has been observed in regions of human brains implicated in schizophrenia (Shi et al, 2014).…”

Section: Mirnas In Schizophreniamentioning

confidence: 98%

“…The SNP rs1801028 (Cys311Ser) in DRD2 is linked to schizophrenia in a metaanalysis (Glatt et al, 2003;Shi et al, 2014). An inverse correlation in the expression of DRD2 and miR-9 has been observed in regions of human brains implicated in schizophrenia (Shi et al, 2014). The pathological significance of miR-9 and miR-124 and their relevant target genes in schizophrenia is worthy of further investigation.…”

Section: Mirnas In Schizophreniamentioning

confidence: 98%

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MicroRNAs: Small molecules with big roles in neurodevelopment and diseases

Sun

Shi

2015

Experimental Neurology

169

116

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MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that play important roles in the development and functions of the brain. Extensive studies have revealed critical roles for miRNAs in brain development and function. Dysregulation or altered expression of miRNAs is associated with abnormal brain development and pathogenesis of neurodevelopmental diseases. This review serves to highlight the versatile roles of these small RNA molecules in normal brain development and their association with neurodevelopmental disorders, in particular, two closely related neuropsychiatric disorders of neurodevelopmental origin, schizophrenia and bipolar disorder.

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Section: Mirnas In Schizophreniamentioning

confidence: 98%

Section: Mirnas In Schizophreniamentioning

confidence: 98%

MicroRNAs: Small molecules with big roles in neurodevelopment and diseases

Sun

Shi

2015

Experimental Neurology

169

116

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“…Gene expression is regulated at the transcriptional and post-transcriptional (RNA decay and protein synthesis) levels, so noncoding variants can influence gene expression through both transcriptional and post-transcriptional regulatory mechanisms [30–32] . Compared to RNA decay, transcription remains the predominant mechanism determining individual expression variation [31] .…”

Section: Gene Regulation As a Causal Molecular Mechanism Underlying Tmentioning

confidence: 99%

Path from schizophrenia genomics to biology: gene regulation and perturbation in neurons derived from induced pluripotent stem cells and genome editing

Duan

2015

Neurosci. Bull.

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Schizophrenia (SZ) is a devastating mental disorder afflicting 1% of the population. Recent genome-wide association studies (GWASs) of SZ have identified >100 risk loci. However, the causal variants/genes and the causal mechanisms remain largely unknown, which hinders the translation of GWAS findings into disease biology and drug targets. Most risk variants are noncoding, thus likely regulate gene expression. A major mechanism of transcriptional regulation is chromatin remodeling, and open chromatin is a versatile predictor of regulatory sequences. MicroRNA-mediated post-transcriptional regulation plays an important role in SZ pathogenesis. Neurons differentiated from patient-specific induced pluripotent stem cells (iPSCs) provide an experimental model to characterize the genetic perturbation of regulatory variants that are often specific to cell type and/or developmental stage. The emerging genome-editing technology enables the creation of isogenic iPSCs and neurons to efficiently characterize the effects of SZ-associated regulatory variants on SZ-relevant molecular and cellular phenotypes involving dopaminergic, glutamatergic, and GABAergic neurotransmissions. SZ GWAS findings equipped with the emerging functional genomics approaches provide an unprecedented opportunity for understanding new disease biology and identifying novel drug targets.

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“…TaqMan genotyping of chr20_43249673_CTCTT_del in the MGS EA sample (2663 cases and 2653 controls) was performed as described previously (72,73) on LightCycler 480 II (Roche). We did not genotype chr20_43254291_T_ins, because the TaqMan custom assay (Life Technologies) could only be designed for chr20_43249673_CTCTT_del.…”

Section: Sanger Sequencing Confirmation and Taqman Genotypingmentioning

confidence: 99%

Transcriptome outlier analysis implicates schizophrenia susceptibility genes and enriches putatively functional rare genetic variants

et al. 2015

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We searched a gene expression dataset comprised of 634 schizophrenia (SZ) cases and 713 controls for expression outliers (i.e., extreme tails of the distribution of transcript expression values) with SZ cases overrepresented compared with controls. These outlier genes were enriched for brain expression and for genes known to be associated with neurodevelopmental disorders. SZ cases showed higher outlier burden (i.e., total outlier events per subject) than controls for genes within copy number variants (CNVs) associated with SZ or neurodevelopmental disorders. Outlier genes were enriched for CNVs and for rare putative regulatory variants, but this only explained a small proportion of the outlier subjects, highlighting the underlying presence of additional genetic and potentially, epigenetic mechanisms.

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MicroRNA-9 and MicroRNA-326 Regulate Human Dopamine D2 Receptor Expression, and the MicroRNA-mediated Expression Regulation Is Altered by a Genetic Variant

Cited by 52 publications

References 82 publications

MicroRNAs: Small molecules with big roles in neurodevelopment and diseases

MicroRNAs: Small molecules with big roles in neurodevelopment and diseases

Path from schizophrenia genomics to biology: gene regulation and perturbation in neurons derived from induced pluripotent stem cells and genome editing

Transcriptome outlier analysis implicates schizophrenia susceptibility genes and enriches putatively functional rare genetic variants

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