Post-transcriptional control of Proliferation, Stress Response & Carcinogenesis

National Institute On Aging

Investigators

Linked publications & trials

Abstract

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 25 years, this Project has examined numerous RBPs, noncoding (nc)RNAs, and their influence on gene expression patterns. We have paid particular attention to their impact 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 linear long noncoding RNAs (lnc)RNAs and circular (circRNAs) 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), many studies in this project use cancer cells as the model system. During this review period, many of these studies have been carried in collaboration with other groups, including those led by Drs. J.-Y. Wang (Ma et al., EMBO Reports 2023) to examine the role of noncoding RNAs promoting homeostasis of the intestinal epithelium. In collaboration with the Franco lab we reported lncRNAs implicated in atrial fibrillation (FASEB J et al., 2022) and we worked with our Sardinian colleagues to report the targets of NF90 (Scientific Reports 2022), genetic variables affecting macular degeneration (Graefe's Archive for Clinical and Experimental Ophthalmology 2023), and GWAS of genetic factors affecting white blood cell morphological parameters (Marongiu et al., Human Molecular Genetics 2022). In another collaboration led by the Lal lab (NCI), we reported the impact of MATRIN3 in mitosis (Cell Reports, 2023). Two major review articles from this period were commissioned to discuss the field of lncRNA biology for the past 25 years (Herman et al., Molecular Cell 2022) and the naming of circular RNAs (Chen et al., Nature Cell Biology, 2023).