Abstract IA04: Control of cell senescence by cancer-associated protein HuR and target noncoding RNAs

Senescent cells accumulate in aging tissues, and their metabolic and gene expression profiles are linked to cancer and other age-associated pathologies. Our recent studies have focused on the cancer-associated RNA-binding protein HuR [1], a suppressor of senescence, and its interaction with different classes of noncoding RNAs—long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs(circRNAs). I discuss the ribonucleoprotein (RNP) complexes that HuR forms with several noncoding RNAs that influence protein abundance and modulate the senescent phenotype. HuR association with lncRNAs such as LINCP21 suppresses the translation of select mRNAs [2], its interaction with lncRNA HOTAIRpromotes the ubiquitin-mediated proteolysis of select proteins [3], and its association with RMRP enhances mitochondrial homeostasis [4], while its competition with 7SL modulates TP53 mRNA translation [5]. Likewise, HuR can bind microRNAs like let-7, which can function as tumor suppressors [6], modulating their availability to repress mRNAs bearing let-7 sites. Finally, our ongoing studies show that HuR can also bind circRNAs, an interaction that reduces the expression of select proliferative proteins and reduces cell division. In summary, HuR is well known for regulating target mRNAs encoding proteins that modulate cancer traits [1], but growing evidence indicates that HuR also regulates many target noncoding RNAs that govern protein expression patterns affecting growth arrest and cell senescence. References: [1] Abdelmohsen and Gorospe, WIRES RNA 2010 [2] Yoon et al., Mol Cell , 2012 [3] Yoon et al., Nat Commun , 2013 [4] Noh et al., Genes Dev, 2016 [5] Abdelmohsen et al., Nucleic Acids Res , 2014 [6] Yoon et al., Genes Dev2015 Citation Format: Kotb Abdelmohsen, Amaresh C. Panda, Ioannis Grammatikakis, Ji Heon Noh, Myriam Gorospe. Control of cell senescence by cancer-associated protein HuR and target noncoding RNAs. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr IA04.