Dr. Chien-hung Yu

EDUCATION
Ph. D., Leiden University, The Netherlands (2011)

RESEARCH INTERESTS
Genetic codes specify amino acids that translates the genetic information (DNA sequences, genotype) into functional output (proteins, phenotype). The three-letter genetic code can be expressed in a simple table with sixty-four entries that represents all twenty amino acids together with three protein synthesis stop signals, which is highly conserved in all living organisms. Most of the amino acids can be decoded by two to six synonymous codons, and these synonyms were thought to be redundant. Intriguingly, the preferential usage of certain synonyms, a phenomenon called codon usage bias, varies in all genomes. The biological functions of codon usage bias are not clear. Our previous work has discovered that codon usage bias plays a significant role in regulating protein structure and function through regulating protein translation dynamics. We further demonstrated that codon usage affects gene expression in both mRNA and protein levels in eukaryotes. These results together strongly suggest that synonymous codons can have strong impact on protein expression levels and function, at least through affecting cotranslational protein folding, without changing the primary peptide sequences. Our lab will use combined molecular, biochemical, genetic, and bioinformatic approaches to understand the mechanisms by which codon usage bias regulates gene expression in eukaryotes. It is of particularly interest to mention that there are accumulating evidences showing silent mutations can cause human diseases. We wish we could tackle these diseases by better understanding how does codon usage affect normal physiological functions.

Publications:

1. Ku, Y. C., Lin, P. H., Huang, C. Y., Lee, C. W., Yu, C.H., Chen, S. C. & Liu, W. M., (2023) An iminocoumarin based covalent-assembly red-emitting fluorescent probe for detection of β-galactosidase activity in ovarian cancer cells. Dyes and Pigments. 210, 111004.


2. Chen, S. Y., Chen, K. L., Ding, L. Y., Yu, C.H., Wu, H. Y., Chou, Y. Y., Chang, C. J., Chang, C. H., Wu, Y. N., Wu, S. R., Hou, Y. C., Lee, C. T., Chen, P. C., Shan, Y. S. & Huang, P. H., (2022) RNA bisulfite sequencing reveals NSUN2-mediated suppression of epithelial differentiation in pancreatic cancer Oncogene. 41, 22, p. 3162-3176 15 p. [Abstract]


3. Yang, T. H., Hsu, C. W., Wang, Y. X., Yu, C.H., Jagat, R., Tseng, Y. Y. & Wu, W. S., (2022) YMLA: A comparative platform to carry out functional enrichment analysis for multiple gene lists in yeast. Computers in Biology and Medicine. 151, 106314. [Abstract]


4. Chen, S. C., Olsthoorn, R. C. L. and Yu, C.H., (2021) Structural phylogenetic analysis reveals lineage-specific RNA repetitive structural motifs in all coronaviruses and associated variations in SARS-CoV-2. Virus Evolution. 7, 1, veab021. [Abstract]


5. Yang, Q., Yu, C.H., Zhao, F., Dang, Y., Wu, C., Xie, P., Sachs, M. S. and Liu, Y., (2019) eRF1 mediates codon usage effects on mRNA translation efficiency through premature termination at rare codons. Nucleic acids research. 47, 17, p. 9243-9258 16 p. [Abstract]


6. Zhao, F., Yu, C.H., and Liu, Y., (2017) Codon usage regulates protein structure and function by affecting translation elongation speed in Drosophila cells Nucleic acids research. 45, 14, p. 8484-8492 9 p. [Abstract]


7. Zhou, Z., Dang, Y., Zhou, M., Li, L., Yu, C.H., Fu, J., Chen, S., and Liu, Y., (2016) Codon usage is an important determinant of gene expression levels largely through its effects on transcription. Proc. Natl. Acad. Sci. U.S.A., 113, E6117-E6125. [Abstract]


8. Yu, C.H.*, Dang, Y.*, Zhou, Z*., Wu, C., Zhao, F., Sachs, M.S., and Liu, Y., (2015) Codon usage influences the local rate of translation elongation to regulate co-translational protein folding. Mol. Cell, 59, 744-754. (*co-first authors) (Cover article and highlighted in TIBS) [Abstract]


9. Yu, C.H. and Olsthoorn, R.C., (2015) Monitoring ribosomal frameshifting as a platform to screen anti-riboswitch drug candidates. Methods Enzymol.,550, 385-393. [Abstract]


10. Yu, C.H. and Olsthoorn, R.C., (2014) Stimulation of ribosomal frameshifting by RNA G-quadruplex structures. Nucleic Acids Res., 42, 1887-1892. [Abstract]


11. Luo, J., Wärmländer, S.K., Yu, C.H., Muhammad, K., Gräslund, A., and Abrahams, J.P., (2014) The Aβ peptide forms non-amyloid fibrils in the presence of carbon nanotubes. Nanoscale., 6(12):6720-6. [Abstract]


12. Luo, J., Otero, J.M., Yu, C.H., Wärmländer, S.K., Gräslund, A., Overhand, M., and Abrahams, J.P., (2013) Inhibiting and reversing amyloid-β peptide (1-40) fibril formation with gramicidin S and engineered analogues. Chemistry, 19, 17338-17348. [Abstract]


13. Luo, J., Yu, C.H., Yu, H., Borstnar, R., Kamerlin, S.C., Gräslund, A., Abrahams, J.P., and Wärmländer, S.K., (2013) Cellular polyamines promote amyloid-beta (Aβ) peptide fibrillation and modulate the aggregation pathways. ACS Chem. Neurosci., 4, 454-62. [Abstract]


14. Yu, C.H. Luo J., Iwata-Reuyl, D., and Olsthoorn, R.C., (2013) Exploiting preQ1 riboswitches to regulate ribosomal frameshifting. ACS Chem. Biol., 8, 733-740. [Abstract]


15. Yu, C.H., Noteborn, M.H., Pleij, C.W., and Olsthoorn, R.C., (2011) Stem-loop structures can effectively substitute for an RNA pseudoknot in -1 ribosomal frameshifting. Nucleic Acids Res., 39, 8952-8959. [Abstract]


16. Yu, C.H., Noteborn, M.H., and Olsthoorn, R.C., (2010) Stimulation of ribosomal frameshifting by antisense LNA. Nucleic Acids Res., 38, 8277-8283. [Abstract]


17. Lien, H.Y., Yu, C.H., Liou, C.M., and Wu, W.F., (2009) Regulation of clpQY (hslVU) Gene Expression in Escherichia coli. Open Microbiol. J., 3, 29-39. [Abstract]


18. Lee, Y.Y., Chang, C.F., Kuo, C.L., Chen, M.C., Yu, C.H., Lin, P.I., and Wu, W.F., (2003) Subunit oligomerization and substrate recognition of the Escherichia coli ClpYQ (HslUV) protease implicated by in vivo protein-protein interactions in the yeast two-hybrid system. J. Bacteriol., 185, 2393-2401. [Abstract]