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  Identification of a long non-coding RNA-associated RNP complex regulating metastasis at the translational step

Gumireddy, K., Li, A., Yan, J., Setoyama, T., Johannes, G. J., Ørom, U. A., et al. (2013). Identification of a long non-coding RNA-associated RNP complex regulating metastasis at the translational step. The EMBO Journal, 32(20), 2672-2684. doi:10.1038/emboj.2013.188.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0019-113D-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0019-113F-6
Genre: Journal Article

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© 2013 European Molecular Biology Organization
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 Creators:
Gumireddy, K., Author
Li, A., Author
Yan, J., Author
Setoyama, T., Author
Johannes, G. J., Author
Ørom, U. A.1, Author              
Tchou, J., Author
Liu, Q., Author
Zhang, L., Author
Speicher, D. W., Author
Calin, G. A., Author
Huang, Q., Author
Affiliations:
1Long non-coding RNA (Ulf Andersson Ørom), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479659              

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Free keywords: Animals Female *Gene Expression Regulation, Neoplastic HEK293 Cells Humans Mice Mice, Inbred NOD Mice, SCID Multiprotein Complexes/metabolism/physiology Neoplasm Metastasis/*genetics Protein Binding Protein Biosynthesis/*genetics RNA, Long Noncoding/*metabolism/physiology Ribonucleoproteins/genetics/isolation & purification/metabolism/*physiology Tumor Cells, Cultured
 Abstract: Long non-coding RNAs (lncRNAs) are a novel class of regulatory genes that play critical roles in various processes ranging from normal development to human diseases such as cancer progression. Recent studies have shown that lncRNAs regulate the gene expression by chromatin remodelling, transcription, splicing and RNA decay control, enhancer function, and epigenetic regulation. However, little is known about translation regulation by lncRNAs. We identified a translational regulatory lncRNA (treRNA) through genome-wide computational analysis. We found that treRNA is upregulated in paired clinical breast cancer primary and lymph-node metastasis samples, and that its expression stimulates tumour invasion in vitro and metastasis in vivo. Interestingly, we found that treRNA downregulates the expression of the epithelial marker E-cadherin by suppressing the translation of its mRNA. We identified a novel ribonucleoprotein (RNP) complex, consisting of RNA-binding proteins (hnRNP K, FXR1, and FXR2), PUF60 and SF3B3, that is required for this treRNA functions. Translational suppression by treRNA is dependent on the 3'UTR of the E-cadherin mRNA. Taken together, our study indicates a novel mechanism of gene regulation by lncRNAs in cancer progression.

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Language(s): eng - English
 Dates: 2013-08-232013-10-16
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: Internal
 Identifiers: DOI: 10.1038/emboj.2013.188
ISSN: 1460-2075 (Electronic)0261-4189 (Print)
URI: http://www.ncbi.nlm.nih.gov/pubmed/23974796
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Title: The EMBO Journal
Source Genre: Journal
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Publ. Info: Nature Publishing Group
Pages: - Volume / Issue: 32 (20) Sequence Number: - Start / End Page: 2672 - 2684 Identifier: ISSN: 0261-4189
CoNE: /journals/resource/954925497061_1