Experimental identification of microRNA targets on the 3′ untranslated region of human FMR1 gene

Yi, Yong‐Hong; Sun, Xunsha; Qin, Jiaming; Zhao, Qi‐Hua; Liao, Wei‐Ping; Long, Yue-Sheng

doi:10.1016/j.jneumeth.2010.04.022

Cited by 25 publications

(18 citation statements)

References 29 publications

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“…Our results also demonstrate that a site-directed mutagenesis spanning 4 bp introduced into the respective seed sequences is effectually disrupting the interaction of miR-518a-5p with the 3′UTR of CCR6. To date, various studies have shown that mutating 3–5 nucleotides is sufficient to disrupt miRNA/mRNA interaction [27]. Mutating more nucleotides or deleting the binding site may achhieve a total repression of miRNA interaction.…”

Section: Discussionmentioning

confidence: 99%

Chemokine receptor CCR6 expression is regulated by miR-518a-5p in colorectal cancer cells

Rubie

Kruse

Frick

et al. 2014

Journal of Translational Medicine

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BackgroundRecently, involvement of the chemokine/receptor system CCL20/CCR6 in colorectal cancer (CRC) progression was shown. Here, we analyzed the functional interaction of miRNA-518-5p (miR-518a-5p) with CCR6 and its impact on CCR6 expression in CRC cells.MethodsMiR-518a-5p was identified by computer software to potentially interact with CCR6. Hence, functional implications of miR-518a-5p with the 3′UTR of CCR6 were analyzed using the Dual Luciferase Reporter assay system. Confirmation of the predicted target site for miR-518a-5p was achieved by site-directed mutagenesis of the seed sequence in the 3′UTR of CCR6 and subsequent application of the mutated seed sequence in a luciferase assay with miR-518a-5p mimics. Accordingly, two CRC cell lines (Caco-2 and HT-29) were transfected with miR-518a-5p miRNA mimics and gene and protein expression of CCR6 was monitored using qRT PCR and immunocytochemistry, respectively.ResultsAddition of miR-518a-5p led to significant down-regulation of luciferase activity (P < 0.05), which was significantly reversed in a reporter test system containing the mutated seed sequences in the 3′UTR of CCR6. Following transfection of CRC cell lines with miR-518a-5p mimics and subsequent monitoring of CCR6 expression showed significant down-regulation of CCR6 mRNA and CCR6 protein expression in both CRC cell lines under investigation (P < 0.05).ConclusionsWe have shown that miR-518a-5p functionally interacts with CCR6 and that transfection of CRC cells with miR-518a-5p leads to significant CCR6 down-regulation. Consequently, CCR6 expression is regulated by miR-518a-5p in CRC cells indicating that regulation of CCR6 expression by miR-518a-5p might be a regulatory mechanism involved in CRC pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Chemokine receptor CCR6 expression is regulated by miR-518a-5p in colorectal cancer cells

Rubie

Kruse

Frick

et al. 2014

Journal of Translational Medicine

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“…The interaction between miRNA and FMRP would mediate miRNA-dependent repression of translation through the RNA interference pathway, by interacting with the components of the RNA-induced silencing complex (RISC) (Jin et al ., 2004). Several defined miRNAs described below have been reported as potential FMRP targets (Yi et al ., 2010) (Table 2). …”

Section: Oligodendrocyte Molecular Targets Modulated By Fmrpmentioning

confidence: 99%

“…Recent research has identified miR-219 as a key molecule in the behavioral manifestations associated with pathophysiology of schizophrenia (Kocerha et al ., 2009), which is related to the abnormal FMRP-dependent Sox expression. Another potential FMRP target is miRNA-338 (Yi et al ., 2010), which is relatively specific to oligodendrocytes and induced with oligodendrocyte differentiation. Its target includes Sox6 and Hes5, which explains why knockdown of miRNA-338 blocks oligodendrocyte differentiation (Zhao et al ., 2010).…”

Section: Oligodendrocyte Molecular Targets Modulated By Fmrpmentioning

confidence: 99%

Altered Translational Control of Fragile X Mental Retardation Protein on Myelin Proteins in Neuropsychiatric Disorders

Jeon

Ryu

Bahn

2017

Biomolecules & Therapeutics

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Myelin is a specialized structure of the nervous system that both enhances electrical conductance and insulates neurons from external risk factors. In the central nervous system, polarized oligodendrocytes form myelin by wrapping processes in a spiral pattern around neuronal axons through myelin-related gene regulation. Since these events occur at a distance from the cell body, post-transcriptional control of gene expression has strategic advantage to fine-tune the overall regulation of protein contents in situ. Therefore, many research interests have been focused to identify RNA binding proteins and their regulatory mechanism in myelinating compartments. Fragile X mental retardation protein (FMRP) is one such RNA binding protein, regulating its target expression by translational control. Although the majority of works on FMRP have been performed in neurons, it is also found in the developing or mature glial cells including oligodendrocytes, where its function is not well understood. Here, we will review evidences suggesting abnormal translational regulation of myelin proteins with accompanying white matter problem and neurological deficits in fragile X syndrome, which can have wider mechanistic and pathological implication in many other neurological and psychiatric disorders.

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“…FMRP is found to be associated with the miRNA processing pathway [92]. miR-19b, miR-302b* and miR-323-3p have been reported to repress the expression of FMRP, suggesting a role of miRNAs in the pathogenesis of Fragile X syndrome [93]. A double-stranded RNA-binding protein DGCR8 is involved in miRNA processing, and functions as an essential Drosha co-factor [94].…”

Section: Mirnas In Neurological Disordersmentioning

confidence: 99%

Functions of Noncoding RNAs in Neural Development and Neurological Diseases

2011

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The development of the central nervous system (CNS) relies on precisely orchestrated gene expression regulation. Dysregualtion of both genetic and environmental factors can affect proper CNS development and results in neurological diseases. Recent studies have shown that similar to protein coding genes, noncoding RNA molecules have a significant impact on normal CNS development and on causes and progression of human neurological disorders. In this review, we have highlighted discoveries of functions of noncoding RNAs, in particular microRNAs and long noncoding RNAs, in neural development and neurological diseases. Emerging evidence has shown that microRNAs play an essential role in many aspects of neural development, such as proliferation of neural stem cells and progenitors, neuronal differentiation, maturation and synaptogenesis. Misregulation of microRNAs is associated with some mental disorders and neurodegeneration diseases. In addition, long noncoding RNAs are found to play a role in neural development by regulating expression of protein coding genes. Therefore, examining noncoding RNA-mediated gene regulations has revealed novel mechanisms of neural development and provided new insights into the etiology of human neurological diseases.

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Experimental identification of microRNA targets on the 3′ untranslated region of human FMR1 gene

Cited by 25 publications

References 29 publications

Chemokine receptor CCR6 expression is regulated by miR-518a-5p in colorectal cancer cells

Chemokine receptor CCR6 expression is regulated by miR-518a-5p in colorectal cancer cells

Altered Translational Control of Fragile X Mental Retardation Protein on Myelin Proteins in Neuropsychiatric Disorders

Functions of Noncoding RNAs in Neural Development and Neurological Diseases

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