In response to external and internal signals, mammalian cells elicit post-transcriptional changes in gene expression patterns that govern the global cellular response. We are keenly interested in the mechanisms that regulate the expression of proliferative, cell cycle-regulatory, and stress-response proteins. Over the past 18 years, this Project has examined numerous RBPs, noncoding (nc)RNAs, and their influence on gene expression patterns. We have paid particular attention to their influence on the stress and proliferative response of cells, two processes that are severely impaired during aging. In the past funding period, we have continued to focus on RBPs implicated in the cellular response to mitogens and stresses, but have expanded substantially into ncRNAs that influence these responses. Since impaired adaptation to mitogens and cell injury underlie various cancer traits (cell proliferation and survival, angiogenesis, invasion, metastasis, and evasion of immune recognition), most studies in this project use cancer cells as the model system. Proliferation and stress response. We have continued to investigate the influence of RBPs and ncRNAs on the homeostasis of the intestinal epithelium, cancer cells and immune cells. During this review period, most of these studies have been carried HuR in collaboration with other groups, including those led by Dr. Jian-Ying Wang (Liu et al., Molecular Biology of the Cell, 2014; Ouyang et al., Biochemical Journal, 2014; Zou et al., American Journal of Physiology, 2015; Liu et al., Molecular Biology of the Cell, 2015; Chung et al., Molecular Medicine 2015; Cao et al., Molecular Biology of the Cell, 2014), Dr. Tom Misteli (Sharma et al., EMBO Reports, 2015) and numerous others. Tumorigenesis. We collaborated with Jonathan Brodys laboratory in the analysis of the role of RBP HuR in pancreatic tumorigenesis (Cozzitorto et al., Methods in Molecular Biology, 2015; McAllister et al., Cancer Biology & Therapy, 2014), and with the group led by Dr. Luiz Penalva in studies of RBP Musashi in glioblastoma (Uren et al., Molecular and Cellular Biology, 2015). Additional work during this review period was aimed at characterizing the ncRNAs involved in cancer, proliferation, stress-response, senescence, and other processes relevant to aging. We compiled the literature pertaining to lncRNAs and RBPs implicated in a range of cellular responses: Yoon et al., (Biochimie, 2014), Yoon et al (Methods in Molecular Biology, 2016), and Yoon et al., (Seminars in Cell and Developmental Biology, 2014).
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