RESEARCH

research-summary

Circular RNAs (circRNAs) are a newly discovered class of RNAs that are generated through back splicing: their 3’ and 5’ ends are joined to form a closed loop. Unlike mRNAs and other linear RNAs, circRNAs lack ends. As a consequence, regulatory elements found on linear RNA, including 5’ caps, 3’ untranslated regions (UTRs), and poly(A) tails are not present on circRNAs. The absence of regulatory features on circRNAs underscores how little is known about these highly-stable RNAs.
Like their linear RNA counterparts, circRNAs exhibit a range of functions within cells. The most notable examples, so far, are as microRNA sponges and as ribosome templates. However, as new circRNA functions continue to be discovered, the regulation of these various functions and their importance in disease remain poorly understood.
We will use a combination of molecular, cellular, genomic, and chemical biology to probe the scope of circRNA function in cells and uncover additional layers of regulation. In particular, we are interested in the movement of circRNAs throughout the cell, their interactions with cellular machinery and metabolites, and regulation of their formation and degradation. We will investigate the impact of RNA secondary structures and post-transcriptional modifications on circRNA function and regulation. Our work will reveal the "life cycle" of circRNAs, establish a cellular atlas of circRNAs, and define the small and macromolecules that contact them. These insights will address a fundamental question in biology of the molecular mechanisms that govern cellular function and provide the platform for developing novel therapies.

PUBLICATIONS

Promoter of lncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element.
Cho SW*, Xu J*, Sun R, Mumbach MR, Carter AC, Chen YG, Yost KE, Kim J, He J, Nevins SA, Chin SF, Caldas C, Liu SJ, Horbeck M, Lim DA, Weissman JS, Curtis C, Chang HY.
Cell (2018). In press.
[FEATURED ARTICLE] Sensing self and nonself circular RNAs by intron identity.
Chen YG, Kim M, Chen X, Batista PJ, Aoyama S, Wilusz JE, Iwasaki A, Chang HY.
Molecular Cell 67, 1-11 (2017).
This paper was presented as a preview in Molecular Cell 67, 163-164 (2017): Antiviral Immunity and Circular RNA: No End in Sight and in Stanford Medicine’s Blog: RNA circles can spur immune response, protect cells against viruses, Stanford researchers find. Also, YG Chen was featured in Molecular Cell’s Meet the Authors.
Mechanisms of immune system gene regulation by long noncoding RNAs.
Chen YG*, Satpathy AT*, Chang HY.
Nature Immunology 18(9): 962-972 (2017).
LncRNA Seduction of GOT2 Goes Viral.
Chen YG and Chang HY
Immunity 47(6): 1021-1023 (2017).
The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline.
Bailey AS*, Batista PJ*, Gold RS, Chen YG, de Rooij DG, Chang HY, Fuller MT
eLife 6:e26116 (2017).
m6A mRNA methylation controls T cell homeostasis by targeting IL-7/STAT5/SOCS pathway.
Li HB*, Tong J*, Zhu S*, Batista PJ, Duffy EE, Zhao J, Bailis W, Guangchao C, Kroehling L, Chen Y, Wang G, Broughton JP, Chen YG, Kluger Y, Simon MD, Chang HY, Yin Z, Flavell RA.
Nature 548, 338–342 (2017).
Discovery and biological characterization of geranylated RNA in bacteria.
Dumelin CE, Chen Y, Leconte AM, Chen YG, Liu DR.
Nature Chemical Biology 8, 913-919 (2012).
LC/MS analysis of cellular RNA reveals NAD-Linked RNA.
Chen YG, Kowtoniuk WE, Agarwal I, Shen Y, Liu DR.
Nature Chemical Biology 5, 879-881 (2009).
Performance assessment and validation of a paramagnetic particle-based enzyme-linked immunosorbent assay for chlorpyrifos in agricultural runoff waters.
Sullivan J, Chen YG, Goh K
J Agric Food Chem 55, 6407-16 (2007).
Oxidative dehydrogenation of dihydropyrimidiones and dihydropyrimidines.
Yamamoto K, Chen YG, Buono F
Organic Letters 7, 4673-4676 (2005).
Kinetic measurements of phosphoglucose isomerase and phosphomannose isomerase by direct analysis of phosphorylated aldose–ketose isomers using tandem mass spectrometry.
Gao H, Chen Y, Leary J
International Journal of Mass Spectrometry 240, 291–299 (2005).

MEMBERS

research-summary

Dr. GRACE CHEN (Principle Investigator)



Dr. Chen received her BS from the University of California, Berkeley in Chemical Biology. She obtained her PhD from Harvard University in Chemical Biology, where she discovered and characterized RNA modifications in Dr. David Liu’s lab. Dr. Chen completed her postdoctoral training at Stanford University in the group of Dr. Howard Chang, where she investigated circular RNA immunity. Dr. Chen will be joining the Department of Immunobiology at Yale University School of Medicine in January 2019.


Want to join us?

RECRUITMENT

The Chen Laboratory is building a dynamic team of collaborative scientists motivated to understand the molecular mechanisms underlying circular RNA function and regulation. Positions at all levels (postdoctoral fellows, graduate students, research associates, and undergraduates) are available. Interested candidates with backgrounds in molecular biology, biochemistry, chemical biology, or genomics should send a cover letter and CV to the PI Dr. Grace Chen at ye.grace.chen (at) yale.edu.