Yi Liu, PhD

Professor
Endowed Title: Louise W. Kahn Scholar in Medical Research 1999-2003
Physiology
Graduate Program: Genetics and Development
Integrative Biology

Contact Information

UT Southwestern Medical Center
5323 Harry Hines Boulevard
Dallas, Texas 75390

Office Phone: 214-645-6033
Office Fax: 214-645-6049

yi.liu@utsouthwestern.edu

Biography

Molecular Mechanisms of RNA Interference and Circadian Clocks

RNA interference and small non-coding RNAs

The production of double-stranded RNA (dsRNA) is known to elicit RNA interference (RNAi) in most eukaryotes and interferon response in mammals. RNAi and related pathways are evolutionarily conserved gene silencing mechanisms that regulate gene expression, development, genome stability, and host-defense responses. The filamentous fungus Neurospora crassa, an organism that broadly employs gene silencing in regulation of gene expression, offers a unique and powerful system for understanding the RNAi pathway and its function in eukaryotes. Using Neurospora as a model system, we have revealed the mechanism of the RISC activation process in the RNAi pathway. We also showed that dsRNA activates a novel signaling pathway to induce transcription of many genes in Neurospora, including most of the RNAi components, putative antiviral genes, and homologs of the interferon stimulated genes; this activation is analogous to the interferon response in mammals. Our current research is focusing on the understanding of the regulation of RNAi components and on the involvement of RNAi pathway in various cellular processes.

Circadian clock

Circadian clocks have been described in almost all organisms ranging in complexity from single cells to mammals and function to control daily rhythms in a variety of biochemical, cellular, physiological and behavioral events. These rhythms have a period close to 24 hours (circadian) and persist in the absence of external time cues. One of the most important characteristics of circadian rhythms is that they can be synchronized or entrained by environmental signals, the strongest of which are light and temperature. In humans and mammals, circadian clocks control events such as sleep-wake and activity cycles, body temperature cycles, endocrine functions, and gene expression. Clinical consequences in humans including sleep disorders and depression can be observed when the clock malfunctions. The influence of a functional clock on temporal regulation is evident from the decreased performance of shift workers and the jet lag felt by long distance travelers.

Our lab is using filamentous fungus Neurospora crassa, one of the best studied model organisms for circadian clocks, to understand the molecular mechanisms of the circadian clock. In Neurospora, the circadian clock acts to control a variety of processes, and previous studies have shown that the Neurospora circadian clock is an auto-regulated negative feedback loop in which the frequency (frq) gene is an essential component.My laboratory is using molecular, biochemical, and genetic approaches to answer three general questions: 1) What are the components of the input pathways to the clock and how do environmental signals entrain the clock; 2) What are the genes that make up the oscillator and how are they regulated to generate rhythms and 3) How does the clock control rhythmic output events? In the long term, these studies will enable us to compare clock mechanisms of fungi with those of other eukaryotes and to help guide research in other organisms.

Education

Graduate SchoolVanderbilt University (1995)
UndergraduateWuhan University - China (1989)

Research Interests

epigenetics
Mechanisms of circadian clocks
non-coding RNAs
RNA interference and gene silencing

Publications

Featured
Diverse pathways generate microRNA-like RNAs and Dicer-independent small interfering RNAs in fungi.

Lee, H.C, L. Li, W. Gu, Z. Xue, S. K. Crosthwaite, A. Pertsemlidis, Z. A. Lewis, M. Freitag, E.U. Selker, C.C. Mello, and Y. Liu. , Molecular Cell (cover article) , 2010; (38):803-814 (cover article)

Featured
The DNA/RNA-dependent RNA polymerase QDE-1 generates aberrant RNA and dsRNA for RNAi in a process requiring Replication Protein A and a DNA helicase

Lee, H.C., A.P. Aalto, Q. Yang, S. Chang, G. Huang, D. Fisher, J. Cha, M.M. Poranen, D.H. Bamford and Y. Liu , PloS Biology , 2010; (8/10):e1000496

Featured
The Exosome Regulates Circadian Gene Expression in a Posttranscriptional Negative Feedback Loop

Guo J, Cheng P, Yuan H and Y Liu , Cell , 2009; (138):1236-1246

Featured
qiRNA is a new type of small interfering RNA induced by DNA damage

Lee HC, Chang SS, Choudhary S, Aalto AP, Maiti M, Bamford DH, Y. Liu. , Nature (cover article) , 2009; (459):274-277. Cover Article

Featured
QIP, a putative exonuclease, interacts with the Neurospora Argonaute protein and facilitates conversion of duplex siRNA into single strands

Maiti, M., Lee, HC., and Liu, Y. , Genes & Development , 2007; (21(5)):590-600

Featured
CKI and CKII mediate the FREQUENCY-dependent phosphorylation of the WHITE COLLAR complex to close the Neurospora circadian negative feedback loop

He, Q., J. Cha, Q. He, H. Lee, Y. Yang, and Y. Liu. , Genes & Development , 2006; (20):2552-2565

Featured
Regulation of the Neurospora circadian clock by an RNA helicase

Cheng, P., Q. He, Q. He, L. Wang, and Y. Liu. , Genes & Development , 2005; (19):234-241

Featured
Distinct roles for PP1 and PP2A in the Neurospora circadian clock.

Yang, Y., Q. He, P. Cheng, P. Wrage, O. Yarden, and Y. Liu. , Genes & Development , 2004; (18):255-260

Featured
Regulation of the Neurospora circadian clock by casein kinase II

Yang, Y., P. Cheng, and Y. Liu. , Genes & Development , 2002; (15):994-1006

Featured
White Collar-1, a DNA-binding transcription factor and a light sensor

He, Q.*, P. Cheng*, Y. Yang, L. Wang, K. H. Gardner, and Y. Liu , Science (cover article) , 2002; (297):840-843

Honors/Awards

1998 - 1999

NIH National Research Service Award for Individual Postdoctoral Fellows

1999 - 2003

Louise W. Kahn Endowed Scholar in Biomedical Research

2004

The Beadle and Tatum Award