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IMP3 RNP safe houses prevent miRNA-directed HMGA2 mRNA decay in cancer and development

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@article{7016777bb8844fe49d8610781b9f68ab,
title = "IMP3 RNP safe houses prevent miRNA-directed HMGA2 mRNA decay in cancer and development",
abstract = "The IMP3 RNA-binding protein is associated with metastasis and poor outcome in human cancer. Using solid cancer transcriptome data, we found that IMP3 correlates with HMGA2 mRNA expression. Cytoplasmic IMP3 granules contain HMGA2, and IMP3 dose-dependently increases HMGA2 mRNA. HMGA2 is regulated by let-7, and let-7 antagomiRs make HMGA2 refractory to IMP3. Removal of let-7 target sites eliminates IMP3-dependent stabilization, and IMP3-containing bodies are depleted of Ago1-4 and miRNAs. The relationship between Hmga2 mRNA and IMPs also exists in the developing limb bud, where IMP1-deficient embryos show dose-dependent Hmga2 mRNA downregulation. Finally, IMP3 ribonucleoproteins (RNPs) contain other let-7 target mRNAs, including LIN28B, and a global gene set enrichment analysis demonstrates that miRNA-regulated transcripts in general are upregulated following IMP3 induction. We conclude that IMP3 RNPs may function as cytoplasmic safe houses and prevent miRNA-directed mRNA decay of oncogenes during tumor progression.",
keywords = "Cell Line, Tumor, Cells, Cultured, Gene Expression Regulation, Neoplastic, HMGA2 Protein, Humans, MicroRNAs, Neoplasms, RNA Stability, RNA, Messenger, RNA-Binding Proteins",
author = "Lars J{\o}nson and Jan Christiansen and Hansen, {Thomas V O} and Jonas Vikes{\aa} and Yohei Yamamoto and Nielsen, {Finn C}",
note = "Copyright {\circledC} 2014 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2014",
month = "4",
day = "24",
doi = "10.1016/j.celrep.2014.03.015",
language = "English",
volume = "7",
pages = "539--51",
journal = "Cell Reports",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - IMP3 RNP safe houses prevent miRNA-directed HMGA2 mRNA decay in cancer and development

AU - Jønson, Lars

AU - Christiansen, Jan

AU - Hansen, Thomas V O

AU - Vikeså, Jonas

AU - Yamamoto, Yohei

AU - Nielsen, Finn C

N1 - Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2014/4/24

Y1 - 2014/4/24

N2 - The IMP3 RNA-binding protein is associated with metastasis and poor outcome in human cancer. Using solid cancer transcriptome data, we found that IMP3 correlates with HMGA2 mRNA expression. Cytoplasmic IMP3 granules contain HMGA2, and IMP3 dose-dependently increases HMGA2 mRNA. HMGA2 is regulated by let-7, and let-7 antagomiRs make HMGA2 refractory to IMP3. Removal of let-7 target sites eliminates IMP3-dependent stabilization, and IMP3-containing bodies are depleted of Ago1-4 and miRNAs. The relationship between Hmga2 mRNA and IMPs also exists in the developing limb bud, where IMP1-deficient embryos show dose-dependent Hmga2 mRNA downregulation. Finally, IMP3 ribonucleoproteins (RNPs) contain other let-7 target mRNAs, including LIN28B, and a global gene set enrichment analysis demonstrates that miRNA-regulated transcripts in general are upregulated following IMP3 induction. We conclude that IMP3 RNPs may function as cytoplasmic safe houses and prevent miRNA-directed mRNA decay of oncogenes during tumor progression.

AB - The IMP3 RNA-binding protein is associated with metastasis and poor outcome in human cancer. Using solid cancer transcriptome data, we found that IMP3 correlates with HMGA2 mRNA expression. Cytoplasmic IMP3 granules contain HMGA2, and IMP3 dose-dependently increases HMGA2 mRNA. HMGA2 is regulated by let-7, and let-7 antagomiRs make HMGA2 refractory to IMP3. Removal of let-7 target sites eliminates IMP3-dependent stabilization, and IMP3-containing bodies are depleted of Ago1-4 and miRNAs. The relationship between Hmga2 mRNA and IMPs also exists in the developing limb bud, where IMP1-deficient embryos show dose-dependent Hmga2 mRNA downregulation. Finally, IMP3 ribonucleoproteins (RNPs) contain other let-7 target mRNAs, including LIN28B, and a global gene set enrichment analysis demonstrates that miRNA-regulated transcripts in general are upregulated following IMP3 induction. We conclude that IMP3 RNPs may function as cytoplasmic safe houses and prevent miRNA-directed mRNA decay of oncogenes during tumor progression.

KW - Cell Line, Tumor

KW - Cells, Cultured

KW - Gene Expression Regulation, Neoplastic

KW - HMGA2 Protein

KW - Humans

KW - MicroRNAs

KW - Neoplasms

KW - RNA Stability

KW - RNA, Messenger

KW - RNA-Binding Proteins

U2 - 10.1016/j.celrep.2014.03.015

DO - 10.1016/j.celrep.2014.03.015

M3 - Journal article

VL - 7

SP - 539

EP - 551

JO - Cell Reports

JF - Cell Reports

IS - 2

ER -

ID: 44845120