Welcome to the Yao Lab
Regulatory non-coding RNAs and RNA-binding proteins (RBPs) are important research areas in gene regulation and RNA biology. Our laboratory is interested in the understanding of pathophysiological function and molecular mechanism of new non-coding RNAs and RBPs and novel modes of translational regulation in cardiac system and cardiovascular disease. We have discovered a new type of stress-responsive, protein-directed human RNA switch that regulates expression of vascular endothelial growth factor-A in human monocytic cells (Ray, PS, et al. Nature 2008 457: 915-919; Yao, P, et al. Plos Biology 2013 11: e1001635) and may play a role in cardiovascular disorders and cancers. Intriguingly, some of these RNA switches involve the interplay between microRNA and RNA-binding protein based on our recent findings (Yao, P, et al. Nucleic Acids Research 2017 45:7950-7964). We also identified a novel mRNA processing mechanism that expands human proteome at the posttranscriptional level and regulates gene expression (Yao, P, et al. Cell 2012 149: 88-100). We are currently asking three major scientific questions for our research: 1) What is the impact of translational control in heart physiology and pathology? 2) What are the molecular mechanisms of translational regulation in cardiac biology? 3) What is the implication of translational regulation in heart disease treatment?
Our current research interests include two aspects:
- Determine the pathophysiological function and regulatory mechanism of noncoding RNAs (e.g., microRNA and regulatory elements in mRNA untranslated regions) and RNA-binding proteins in cardiac system and cardiovascular disorders:
We are currently investigating the cardioprotective function and molecular mechanisms of mammalian miR-574 in cardiac hypertrophy and pathological remodeling. In this research program, we have discovered that in cardiac cells dual-strand miRNA miR-574-5p and miR-574-3p target a potential translation regulatory factor in mitochondria, FAM210A, thereby maintaining mitochondrial translational homeostasis and preventing cardiac hypertrophy and ventricular remodeling.
- Elucidate the role of translation machinery and translational control in cardiovascular system and identify therapeutic targets for treatment of cardiac diseases:
We have recently discovered that multiple cardiac stresses induce the expression of glutamyl-prolyl-tRNA synthetase (EPRS) that promotes cardiac fibrosis via increased Pro-tRNAPro pool and consequent translation of pro-fibrotic proline codon rich mRNAs (e.g., collagens, LTBP2, SULF1 among others) in cardiac fibroblasts using genome-wide polysome-seq and RNA-seq. This project will provide new insights into the translational control mechanisms in cardiac fibrosis and identify novel disease markers and therapeutic targets to treat heart disease.
We employ various approaches and methods of biochemistry and biophysics, molecular and cellular biology, genetic and surgical mouse models, as well as bioinformatic analytic tools to dissect the convergent and divergent regulatory pathways. The long-term objective of our laboratory is to identify novel translation-related molecular mechanisms that control gene expression and conduct pathophysiological function in cardiac system, as well as to develop novel therapeutic approaches for the prevention or treatment of human cardiovascular diseases.