Kontrolle der Funktion von mRNA-bindenden Proteinen und mRNPs durch Y RNAs
Allgemeine Genetik und funktionelle Genomforschung
Evolutionäre Zell- und Entwicklungsbiologie der Tiere
Zusammenfassung der Projektergebnisse
The project aimed at characterizing the role of non-coding Y RNAs in scaffolding and/or disturbing regulatory mRNPs in the cytoplasm of cancer cells by associating with RNA binding proteins. This hypothesis was derived from prior studies in which we demonstrated that Y RNAs, in particular Y3**, serve roles in the 3’-end processing of histone mRNAs in the nucleus by recruiting RNA regulatory RBPs like CPSF (3). However, especially the Y3 RNA is mainly observed in the cytoplasm where it associates with various RBPs, e.g. IGF2BPs (IMPs) and ELAVLs (HuRs) via its single stranded loop and the Ro60 (TROVE2) protein associating at a bulge in the Y RNA’s stem. In collaboration with the Quattrone lab, we demonstrated that the Y3 RNA decoys the HuD protein in neural cells, in particular motor neurons. In agreement with the role of HuD in enhancing mRNA translation in an mTORC1-dependent manner, Y3 RNA directed decoy of HuD led to severely impaired translation of various mRNAs encoding factors implicated in neural differentiation. Studies aiming at demonstrating that this decoy function is also observed for other RBPs like IGF2BP1 largely failed up to this point. However, during the aforementioned studies, we have established novel approaches to identify medium sized non-coding RNAs (ncRNAs) by RNA-sequencing and specialized data analysis pipelines. This allowed the identification of various novel medium sized ncRNAs, including several prior unknown POLIII-driven transcripts. These are currently investigated, next to Y RNAs, by the lab of Marcel Köhn, who established his independent research profile based on these original findings and explores the role of ncRNAs and RBPs in guiding gene expression in cardiovascular diseases and cancer.
Projektbezogene Publikationen (Auswahl)
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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, David; Hüttelmaier, Stefan & Quattrone, Alessandro
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POLIII-derived non-coding RNAs acting as scaffolds and decoys. Journal of Molecular Cell Biology, 11(10), 880-885.
Täuber, Hendrik; Hüttelmaier, Stefan & Köhn, Marcel
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Identification and initial characterization of POLIII-driven transcripts by msRNA-sequencing. RNA Biology, 18(11), 1807-1817.
Zorn, Peter; Misiak, Danny; Gekle, Michael & Köhn, Marcel
