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

First Author  Gumireddy K Year  2013
Journal  EMBO J Volume  32
Issue  20 Pages  2672-84
PubMed ID  23974796 Mgi Jnum  J:202484
Mgi Id  MGI:5519173 Doi  10.1038/emboj.2013.188
Citation  Gumireddy K, et al. (2013) Identification of a long non-coding RNA-associated RNP complex regulating metastasis at the translational step. EMBO J 32(20):2672-84
abstractText  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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