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Identification of a long non‐coding RNA‐associated RNP complex regulating metastasis at the translational step
Author(s) -
Gumireddy Kiranmai,
Li Anping,
Yan Jinchun,
Setoyama Tetsuro,
Johannes Gregg J,
Ørom Ulf A,
Tchou Julia,
Liu Qin,
Zhang Lin,
Speicher David W,
Calin George A,
Huang Qihong
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2013.188
Subject(s) - biology , identification (biology) , rna , computational biology , genetics , microbiology and biotechnology , gene , ecology
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 re gulatory lnc RNA (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.