<scp>RNA</scp>
            Interference: Mechanisms and Proteins Involved

Wang, Wang‐Xia; Nelson, Peter T.; Tang, Guiliang

doi:10.1002/9780470048672.wecb517

Cited by 3 publications

(4 citation statements)

References 134 publications

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“…These observations are compatible with the hypothesis that a distinct mechanism other than stable AGO association is involved in miR-107:BACE1 regulation. Given the known multiple avenues of miRNA-based gene expression regulation, 17,93,95 these results suggest that there are alternative pathways of miR-107 gene expression regulation. These pathways are a focus of ongoing research in our laboratory and may involve "slicing" or destabilization of BACE1 mRNA, a more tenuous association between BACE1 mRNA and AGO, or some other mechanism(s).…”

Section: Discussionmentioning

confidence: 90%

“…AGO-miRNPs have been shown to exert gene expression regulation via multiple mechanisms. 17,93 For the mRNA to be "read out" on a microarray downstream of the anti-Ago co-IP, the target mRNA must be stably bound to the miRNP. When AGO2 works as a "slicer" to enzymatically cleave target mRNAs, 94 one would expect a less stable miRNA:mRNA association and hence lower yield of mRNA targets.…”

Section: Discussionmentioning

confidence: 99%

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miR-107 Regulates Granulin/Progranulin with Implications for Traumatic Brain Injury and Neurodegenerative Disease

Wang

Wilfred

Madathil

et al. 2010

The American Journal of Pathology

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167

134

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Granulin (GRN, or progranulin) is a protein involved in wound repair, inflammation, and neoplasia. GRN has also been directly implicated in frontotemporal dementia and may contribute to Alzheimer's disease pathogenesis. However, GRN regulation expression is poorly understood. A high-throughput experimental microRNA assay showed that GRN is the strongest target for miR-107 in human H4 neuroglioma cells. miR-107 has been implicated in Alzheimer's disease pathogenesis, and sequence elements in the open reading frame-rather than the 3 untranslated region-of GRN mRNA are recognized by miR-107 and are highly conserved among vertebrate species. To better understand the mechanism of this interaction, FLAG-tagged Argonaute constructs were used following miR-107 transfection. GRN mRNA interacts preferentially with Argonaute 2. In vitro and in vivo studies indicate that regulation of GRN by miR-107 may be functionally important. Glucose supplementation in cultured cells that leads to increased miR-107 levels also results in decreased GRN expression , including changes in cell compartmentation and decreased secretion of GRN protein. This effect was eliminated following miR-107 transfection. We also tested a mouse model where miR-107 has been shown to be down-regulated. In brain tissue subjacent to 1.0 mm depth controlled cortical impact , surviving hippocampal neurons show decreased miR-107 with augmentation of neuronal GRN expression. These findings indicate that miR-107 contributes to GRN expression regulation with implications for brain disorders.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

miR-107 Regulates Granulin/Progranulin with Implications for Traumatic Brain Injury and Neurodegenerative Disease

Wang

Wilfred

Madathil

et al. 2010

The American Journal of Pathology

Self Cite

167

134

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“…Aside from the inherent limitations of the cultured tumor cells, RIP-Chip is an assay that does not provide all the information about miRNA:mRNA interactions. AGO-miRNPs have been shown to exert gene expression regulation via multiple mechanisms ( 1 , 39 ). For the mRNA target to be detected by a microarray downstream of the anti-Ago co-IP, the target mRNA must be stably bound to the miRNP which is not necessarily expected in all modes of mRNA translational repression.…”

Section: Discussionmentioning

confidence: 99%

Specific sequence determinants of miR-15/107 microRNA gene group targets

Nelson

Wang

Mao

et al. 2011

Nucleic Acids Research

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MicroRNAs (miRNAs) target mRNAs in human cells via complex mechanisms that are still incompletely understood. Using anti-Argonaute (anti-AGO) antibody co-immunoprecipitation, followed by microarray analyses and downstream bioinformatics, ‘RIP-Chip’ experiments enable direct analyses of miRNA targets. RIP-Chip studies (and parallel assessments of total input mRNA) were performed in cultured H4 cells after transfection with miRNAs corresponding to the miR-15/107 gene group (miR-103, miR-107, miR-16 and miR-195), and five control miRNAs. Three biological replicates were run for each condition with a total of 54 separate human Affymetrix Human Gene 1.0 ST array replicates. Computational analyses queried for determinants of miRNA:mRNA binding. The analyses support four major findings: (i) RIP-Chip studies correlated with total input mRNA profiling provides more comprehensive information than using either RIP-Chip or total mRNA profiling alone after miRNA transfections; (ii) new data confirm that miR-107 paralogs target coding sequence (CDS) of mRNA; (iii) biochemical and computational studies indicate that the 3′ portion of miRNAs plays a role in guiding miR-103/7 to the CDS of targets; and (iv) there are major sequence-specific targeting differences between miRNAs in terms of CDS versus 3′-untranslated region targeting, and stable AGO association versus mRNA knockdown. Future studies should take this important miRNA-to-miRNA variability into account.

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“…Aside from the inherent limitations of the cultured tumor cells, RIP-Chip is an assay that does not provide all the information about miRNA:mRNA interactions. AGO-miRNPs have been shown to exert gene expression regulation via multiple mechanisms 1,3. For the mRNA target to be detected by a microarray downstream of the anti-Ago co-IP, the target mRNA must be stably bound to the miRNP.…”

Section: Discussionmentioning

confidence: 99%