The role of the RO60 (TROVE2) autoantigen in modulating cell-cycle progression, apoptosis and chemo-resistance in cancer cells
Final Report Abstract
The main goal of the proposed studies was to characterize the role of the RO60 protein (TROVE2) in cancer-derived cells. These studies settled on the finding that the transient depletion of RO60 by siRNA pools impaired the p53-dependent upregulation of p21 synthesis. Although these findings could not be confirmed probably due to off-target effects, the studies led to the characterization of a novel role of the RO60-associated Y RNAs. For the Y3** ncRNA derived from the RO60-associated Y3 RNA we could identify a role in the 3'-end processing of canonical histone mRNAs. Moreover, the analyses set the stage for addressing the role of RO60-associated cytoplasmic Y RNAs in modulating the role of RNA-binding proteins controlling mRNA translation and/or turnover currently funded by the SPP1935. Collaborative efforts with the Quattrone lab (Trento, Italy) support the initial hypothesis proposing a role of Y RNAs in serving as decoys of specific RNA-binding proteins.
Publications
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(2018) HuD Is a Neural Translation Enhancer Acting on mTORC1-Responsive Genes and Counteracted by the Y3 Small Non-coding RNA. Molecular cell 71 (2) 256-270.e10
Tebaldi, Toma; Zuccotti, Paola; Peroni, Daniele; Köhn, Marcel; Gasperini, Lisa; Potrich, Valentina; Bonazza, Veronica; Dudnakova, Tatiana; Rossi, Annalisa; Sanguinetti, Guido; Conti, Luciano; Macchi, Paolo; D'Agostino, Vito; Viero, Gabriella; Tollervey, D
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The Y3** ncRNA promotes the 3' end processing of histone mRNAs. Genes Dev. 2015 Oct 1;29(19):1998-2003
Kohn M, Ihling C, Sinz A, Krohn K, Huttelmaier S
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Non-coding RNAs, the cutting edge of histone messages. RNA Biol. 2016 Feb 24:1-6
Kohn M, Huttelmaier S
