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Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay.

Molecular cell | May 19, 2011 |

Bruno, Ivone G | Karam, Rachid | Huang, Lulu | Bhardwaj, Anjana | Lou, Chih H | Shum, Eleen Y | Song, Hye-Won | Corbett, Mark A | Gifford, Wesley D | Gecz, Jozef | Pfaff, Samuel L | Wilkinson, Miles F
Bruno, Karam, et al. "Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay." Molecular cell 42.4 (2011): 500-10. Web.

Abstract

Nonsense-mediated decay (NMD) degrades both normal and aberrant transcripts harboring stop codons in particular contexts. Mutations that perturb NMD ca ... suggest the existence of a conserved RNA circuit linking the microRNA and NMD pathways that induces cell type-specific transcripts during development.

Nonsense-mediated decay (NMD) degrades both normal and aberrant transcripts harboring stop codons in particular contexts. Mutations that perturb NMD cause neurological disorders in humans, suggesting that NMD has roles in the brain. Here, we identify a brain-specific microRNA-miR-128-that represses NMD and thereby controls batteries of transcripts in neural cells. miR-128 represses NMD by targeting the RNA helicase UPF1 and the exon-junction complex core component MLN51. The ability of miR-128 to regulate NMD is a conserved response occurring in frogs, chickens, and mammals. miR-128 levels are dramatically increased in differentiating neuronal cells and during brain development, leading to repressed NMD and upregulation of mRNAs normally targeted for decay by NMD; overrepresented are those encoding proteins controlling neuron development and function. Together, these results suggest the existence of a conserved RNA circuit linking the microRNA and NMD pathways that induces cell type-specific transcripts during development.

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Nihms293798f1
Fig 1. Bruno, Karam, et al. "Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay." Molecular cell 42.4 (2011): 500-10. Web.
Nihms293798f1
Fig 1. Bruno, Karam, et al. "Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay." Molecular cell 42.4 (2011): 500-10. Web.

Fig 1

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Nihms293798f2
Fig 2. Bruno, Karam, et al. "Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay." Molecular cell 42.4 (2011): 500-10. Web.
Nihms293798f2
Fig 2. Bruno, Karam, et al. "Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay." Molecular cell 42.4 (2011): 500-10. Web.

Fig 2

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Nihms293798f3
Fig 3. Bruno, Karam, et al. "Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay." Molecular cell 42.4 (2011): 500-10. Web.
Nihms293798f3
Fig 3. Bruno, Karam, et al. "Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay." Molecular cell 42.4 (2011): 500-10. Web.

Fig 3

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Nihms293798f4
Fig 4. Bruno, Karam, et al. "Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay." Molecular cell 42.4 (2011): 500-10. Web.
Nihms293798f4
Fig 4. Bruno, Karam, et al. "Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay." Molecular cell 42.4 (2011): 500-10. Web.

Fig 4

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Nihms293798f5
Fig 5. Bruno, Karam, et al. "Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay." Molecular cell 42.4 (2011): 500-10. Web.
Nihms293798f5
Fig 5. Bruno, Karam, et al. "Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay." Molecular cell 42.4 (2011): 500-10. Web.

Fig 5

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Fig 6. Bruno, Karam, et al. "Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay." Molecular cell 42.4 (2011): 500-10. Web.
Nihms293798f6
Fig 6. Bruno, Karam, et al. "Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay." Molecular cell 42.4 (2011): 500-10. Web.

Fig 6

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