Topics
We are broadly interested in the role of RNA in cell physiology and disease. Unlike DNAs or proteins, RNAs are both carriers of genetic information and functional molecules, making them versatile players in biology. In the Shi lab, we focuses on the processes of how RNAs are made and how they are degraded.
RNA processing:
Although the human genome only contains 20,000~25,000 genes, much greater number of transcripts can be made through alternative RNA processing, including alternative splicing (AS) and alternative polyadenylation (APA). AS and APA are highly regulated in development and mis-regulation of these processes cause many human diseases. Current projects in the lab on this topic include:
- Biochemical and structural analyses of cleavage/polyadenylation complex
- Regulation of AS and APA in virus-host interactions, immune response, and stem cell differentiation
- Functional analyses of AS or APA in development using human iPSC and mouse models
- Drug development and characterization targeting APA
RNA degradation:
RNA degradation is critical for surveillance (mis-processed RNA must be quickly removed) and regulation of gene expression. Aberrant RNA degradation, including abnormal degradation of essential RNAs and accumulation of harmful RNAs due to lack of degradation, cause a large number of diseases, including ALS, Huntington’s disease, and many rare genetic disorders. Current projects in the lab on this topic include:
- RNA degradation specificity: although many RNA degradation enzymes have been identified, it remains unclear how they recognize their specific targets. We recently discovered a nuclear RNA degradation code mechanism that explains how RNA degradation specificity is determined. We are currently in the process of fully deciphering this code.
- Identify regulators of RNA degradation
- Develop therapeutic tools for diseases caused by aberrant RNA degradation
Approaches:
- Biochemical and structural analyses
- Cell biology
- Genomics
- Artificially intelligence
- Disease modeling using human embryonic stem cells and iPS cells
- Mouse models