title: Identification of a long non-coding RNA-associated RNP complex regulating metastasis at the translational step.
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.
authors: The Wistar Institute, Philadelphia, PA, USA.
authors: Kiranmai
authors: K
authors: Gumireddy
authors: Anping
authors: A
authors: Li
authors: Jinchun
authors: J
authors: Yan
authors: Tetsuro
authors: T
authors: Setoyama
authors: Gregg J
authors: GJ
authors: Johannes
authors: Ulf A
authors: UA
authors: Orom
authors: Julia
authors: J
authors: Tchou
authors: Qin
authors: Q
authors: Liu
authors: Lin
authors: L
authors: Zhang
authors: David W
authors: DW
authors: Speicher
authors: George A
authors: GA
authors: Calin
authors: Qihong
authors: Q
authors: Huang
mesh_terms: D000818:Animals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D046912:Multiprotein Complexes / Q000378:metabolism / Q000502:physiology; D009362:Neoplasm Metastasis / Q000235:genetics*; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000378:metabolism* / Q000502:physiology; D012261:Ribonucleoproteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D046912:Multiprotein Complexes; D062085:RNA, Long Noncoding; D012261:Ribonucleoproteins
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