RNA Regulation Section
Myriam Gorospe, Ph.D., Chief
The mission of the RNA Regulation Section (RRS), led by Myriam Gorospe, is to investigate the post-transcriptional mechanisms that regulate gene expression in aging physiology and pathology. The Section is particularly interested in the control of mRNA processing, transport, turnover, and translation by RNA-binding proteins (RBPs) and noncoding RNAs (ncRNAs). The general working hypothesis in the RRS is that post-transcriptional gene regulation directly impacts upon the normal physiologic decline of aging as well as the aberrant gene expression programs in age-associated disease. The Section is testing this hypothesis in normal aging processes by analyzing the impact of RBPs and ncRNAs on age-associated inflammation, impaired muscle regeneration, cellular senescence, and declining responses to proliferative and metabolic stimuli. The Section is also investigating this hypothesis in age-associated diseases such as diabetes, obesity, sarcopenia, neurodegeneration, and cancer, by testing the impact of RBPs and ncRNAs on post-transcriptional gene regulation in pathologies of aging.
List of Portfolio/Research Areas
Using a range of cell models of aging-associated declines and diseases, the RRS studies the function of RBPs and ncRNAs in four main research areas:
- Cell senescence, including gene expression programs and function of senescent cells, and the senescence-associated secretory phenotype (SASP)
- Energy metabolism, focusing on organelles (mitochondria) and cells (pancreatic cells, muscle cells, and neurons) that store, sense, mobilize, create and use energy
- Cellular response to stress, with a focus on DNA damage, oxidative stress, and nutrient deprivation
- Neurodegeneration, through the analysis of gene expression program and cell types implicated in neurodegenerative processes.
Findings and Publications
Abdelmohsen K, Panda A, Kang MJ, Xu J, Selimyan R, Yoon JH, De S, Wood WH3rd, Becker KG, Gorospe M. Senescence associated lncRNAs: Senescence-associated long noncoding RNAs. Aging Cell 12:890-900, 2013.
Kang MJ, Abdelmohsen K, Hutchison ER, Mitchell SJ, Grammatikakis I, Guo R, Noh JH, Martindale JL, Yang X, Lee EK, Faghihi MA, Wahlestedt C, Troncoso JC, Perrone-Bizzozero N, Resnick SM, de Cabo R, Mattson MP, Gorospe M. HuD regulates coding and noncoding RNA to induce APP Aβ processing. Cell Reports 7:1401-1409, 2014.
Yoon JH, De S, Hafner M, Srikantan S, Abdelmohsen K, Grammatikakis I, Kim J, Kim KM, Noh JH, White EJF, Martindale JL, Yang X, Kang MJ, Wood WH3rd, Noren Hooten N, Evans MK, Becker KG, Tripathi V, Prasanth KV, Wilson GM, Tuschl T, Ingolia NT, Gorospe M. PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity.
Nature Communications 5:5248, 2014.
Yoon JH, Jo MH, White EJF, De S, Hafner M, Zucconi BE, Abdelmohsen K, Martindale JL, Yang X, Wood WH3rd, Shin YM, Song JJ, Tuschl T, Becker KG, Wilson GM, Hohng S, Gorospe M. AUF1 promotes let-7b loading on Argonaute 2. Genes & Development 29:1599-604, 2015.
Noh JH, Kim KM, Abdelmohsen K, Yoon JH, Panda AC, Munk R, Kim J, Curtis J, Moad CA, Wohler CM, Indig FE, de Paula W, Dudekula DB, Piao Y, De S, Yang X, Martindale JL, de Cabo R, Gorospe M. HuR and GRSF1 modulate the nuclear export and mitochondrial localization of lncRNA RMRP. Genes & Development 30:1224-1239, 2016.