MicroRNAs Regulate Brain Morphogenesis in Zebrafish

Giráldez, Antonio J.; Cinalli, Ryan M.; Glasner, Margaret E.; Enright, Anton J.; Thomson, J. Michael; Baskerville, Scott; Hammond, Scott M.; Bartel, David P.; Schier, Alexander F.

doi:10.1126/science.1109020

Cited by 1,195 publications

(1,080 citation statements)

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“…The alternative explanation, that in these species an essential RNAi role(s) was compensated by another mechanism, would require the independent evolution of the latter multiple times. Moreover, in organisms that contain a single Dicer gene such as S. pombe and vertebrates, Dicer-null mutants are RNAi-defective but viable at the cellular level (Giraldez et al 2005;Kanellopoulou et al 2005;Martienssen et al 2005;Murchison et al 2005;Volpe et al 2002). Though these mutants commonly show reactivation of transposons and/or repetitive sequences, deficient (hetero)chromatin formation, and/or abnormal chromosome segregation; and vertebrate germ cells fail to differentiate (Fukagawa et al 2004;Kanellopoulou et al 2005;Martienssen et al 2005;Murchison et al 2005).…”

Section: Nature Of the Ancestral Rnai Machinerymentioning

confidence: 99%

“…In contrast, miRNAs are essential for the development of animals and plants (Bartel 2004;Kidner and Martienssen 2005;Wienholds and Plasterk 2005). For instance Dicer-deficient vertebrate germ cells are viable but they fail to differentiate (Giraldez et al 2005;Kanellopoulou et al 2005;Murchison et al 2005). Moreover, Dicer is required for morphogenesis (but not for cell fate specification) during zebrafish embryogenesis, and the absence of miRNAs is responsible, at least in part, for this phenotype (Giraldez et al 2005).…”

Section: Additional (Derived?) Functions Of the Rnai Machinerymentioning

confidence: 99%

“…For instance Dicer-deficient vertebrate germ cells are viable but they fail to differentiate (Giraldez et al 2005;Kanellopoulou et al 2005;Murchison et al 2005). Moreover, Dicer is required for morphogenesis (but not for cell fate specification) during zebrafish embryogenesis, and the absence of miRNAs is responsible, at least in part, for this phenotype (Giraldez et al 2005). Similarly, null alleles of Dicer-like1, necessary for the generation of mature miRNAs, result in embryo lethality in A. thaliana Ray et al 1996;Kidner and Martienssen 2005).…”

Section: Additional (Derived?) Functions Of the Rnai Machinerymentioning

confidence: 99%

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On the origin and functions of RNA-mediated silencing: from protists to man

2006

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Double-stranded RNA has been shown to induce gene silencing in diverse eukaryotes and by a variety of pathways. We have examined the taxonomic distribution and the phylogenetic relationship of key components of the RNA interference (RNAi) machinery in members of five eukaryotic supergroups. On the basis of the parsimony principle, our analyses suggest that a relatively complex RNAi machinery was already present in the last common ancestor of eukaryotes and consisted, at a minimum, of one Argonautelike polypeptide, one Piwi-like protein, one Dicer, and one RNAdependent RNA polymerase. As proposed before, the ancestral (but non-essential) role of these components may have been in defense responses against genomic parasites such as transposable elements and viruses. From a mechanistic perspective, the RNAi machinery in the eukaryotic ancestor may have been capable of both small-RNA-guided transcript degradation as well as transcriptional repression, most likely through histone modifications. Both roles appear to be widespread among living eukaryotes and this diversification of function could account for the evolutionary conservation of duplicated Argonaute-Piwi proteins. In contrast, additional RNAi-mediated pathways such as RNA-directed DNA methylation, programmed genome rearrangements, meiotic silencing by unpaired DNA, and miRNA-mediated gene regulation may have evolved independently in specific lineages.

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Section: Nature Of the Ancestral Rnai Machinerymentioning

confidence: 99%

Section: Additional (Derived?) Functions Of the Rnai Machinerymentioning

confidence: 99%

Section: Additional (Derived?) Functions Of the Rnai Machinerymentioning

confidence: 99%

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On the origin and functions of RNA-mediated silencing: from protists to man

2006

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“…The majority of the putative targets have only a single miRNA-binding site for individual miRNAs which probably is non-sufficient for governing switch type regulation. Furthermore, inhibitions of all miRNAs by depleting Dicer do not severely impair differentiation and patterning in vertebrates (Giraldez et al, 2005;Harfe et al, 2005). Indeed, miRNAs have recently been hypothesized to be part of genetic networks wired by feed-forward loops that maintain the fidelity of developmental programs, rather than initiating developmental transitions, by conferring robustness with both preventing leaky transcriptions and buffering genetic noise (Hornstein and Shomron, 2006).…”

Section: Global Effects Of Mirnas On Gene Expressionmentioning

confidence: 99%

Principles and effects of microRNA-mediated post-transcriptional gene regulation

2006

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MicroRNAs (miRNAs) are abundant regulatory RNAs involved in the regulation of many key biological processes. Recent advances in understanding the mechanism of RNA interference and miRNA-mediated mechanisms shed light on major principals of the formation of the regulatory complex and provide models to explain how these small regulatory RNA species interfere with gene expression and how they influence the translational status of the transcriptome.

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“…Approximately 50% of mammalian miRNAs are expressed in the brain (Krichevsky et al ., 2003; Somel et al ., 2011), many of which have critical roles in neurogenesis and neuronal development (Giraldez et al ., 2005; De Pietri Tonelli et al ., 2008). A number of hippocampal miRNAs regulate neuronal activity by targeting their downstream genes (Eacker et al ., 2011; Juhila et al ., 2011).…”

Section: Introductionmentioning

confidence: 99%

miR‐204 downregulates EphB2 in aging mouse hippocampal neurons

et al. 2016

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SummaryHippocampal synaptic function and plasticity deteriorate with age, often resulting in learning and memory deficits. As MicroRNAs (miRNAs) are important regulators of neuronal protein expression, we examined whether miRNAs may contribute to this age‐associated decline in hippocampal function. We first compared the small RNA transcriptome of hippocampal tissues from young and old mice. Among 269 hippocampal miRNAs, 80 were differentially expressed (≥ twofold) among the age groups. We focused on 36 miRNAs upregulated in the old mice compared with those in the young mice. The potential targets of these 36 miRNAs included 11 critical Eph/Ephrin synaptic signaling components. The expression levels of several genes in the Eph/Ephrin pathway, including EphB2, were significantly downregulated in the aged hippocampus. EphB2 is a known regulator of synaptic plasticity in hippocampal neurons, in part by regulating the surface expression of the NMDA receptor NR1 subunit. We found that EphB2 is a direct target of miR‐204 among miRNAs that were upregulated with age. The transfection of primary hippocampal neurons with a miR‐204 mimic suppressed both EphB2 mRNA and protein expression and reduced the surface expression of NR1. Transfection of miR‐204 also decreased the total expression of NR1. miR‐204 induces senescence‐like phenotype in fully matured neurons as evidenced by an increase in p16‐positive cells. We suggest that aging is accompanied by the upregulation of miR‐204 in the hippocampus, which downregulates EphB2 and results in reduced surface and total NR1 expression. This mechanism may contribute to age‐associated decline in hippocampal synaptic plasticity and the related cognitive functions.

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MicroRNAs Regulate Brain Morphogenesis in Zebrafish

Cited by 1,195 publications

References 39 publications

On the origin and functions of RNA-mediated silencing: from protists to man

On the origin and functions of RNA-mediated silencing: from protists to man

Principles and effects of microRNA-mediated post-transcriptional gene regulation

miR‐204 downregulates EphB2 in aging mouse hippocampal neurons

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