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Type: Journal article
Title: Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay
Author: Bruno, I.
Karam, R.
Huang, L.
Bhardwaj, A.
Lou, C.
Shum, E.
Song, H.
Corbett, M.
Gifford, W.
Gecz, J.
Pfaff, S.
Wilkinson, M.
Citation: Molecular Cell, 2011; 42(4):500-510
Publisher: Cell Press
Issue Date: 2011
ISSN: 1097-2765
Statement of
Ivone G. Bruno, Rachid Karam, Lulu Huang, Anjana Bhardwaj, Chih H. Lou, Eleen Y. Shum, Hye-Won Song, Mark A. Corbett, Wesley D. Gifford, Jozef Gecz, Samuel L. Pfaff, and Miles F. Wilkinson
Abstract: 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.
Keywords: Brain
Hela Cells
Chick Embryo
Xenopus laevis
RNA Helicases
RNA-Binding Proteins
Neoplasm Proteins
Nuclear Proteins
Oligonucleotide Array Sequence Analysis
Gene Expression Regulation, Developmental
RNA Stability
Transcriptional Activation
HEK293 Cells
Rights: Copyright © 2011 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.molcel.2011.04.018
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