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 24 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 (Xiao et al., Gastroenterology 2021) to examine the role of circular RNA circHIPK3 in promoting homeostasis of the intestinal epithelium by reducing miR-29b function. In collaboration with the Biswas lab (USUHS) we reported that SFPQ rescues F508del-CFTR expression and function in cystic fibrosis bronchial epithelial cells (Kumar et al., Scientific Reports 2021). Collaborations with groups in Sardinia have resulted in reports that systematic assessed NF90 targets by iCLIP analysis (Lodde et al., Scientific Reports, 2022) and GWAS studies revealing genetic factors affecting white blood cell morphological parameters (Marongiu et al., Human Molecular Genetics 2022). A major review article from this period was commissioned to discuss the past 25 years of lncRNA biology (Herman et al., Molecular Cell 2022).