Hanna's Lab



Cho&, C.-C., Lin&, C.-J., Huang, H.-H., Yang, W.-Z., Lin, H.-Y., Lee*, M.-S. and Yuan*, H. S. (2023)
Molecular mechanism underlying harmine-mediated inhibition of human DNA methyltransferases and prostate cancer cell growth.
ACS Chem. Biol. 18, 1335-1350 (2023).


Jain, M., Golzarroshan, B., Lin, C.-L., Agrawal, S., Tang, W.-H., Wu, C.-J. and Yuan*, H. S. (2022)
Dimeric assembly of human Suv3 helicase promotes its RNA unwinding function in mitochondrial RNA degradosome for RNA decay.
Prot. Sci. 31, 5, e4312 (2022).

Chen, T., Grauffel, C, Yang, W.-Z., Chen, Y. P., Yuan*, H. S. and Lim*, C. (2022)
An efficient strategy to design protease inhibitors: Application to Enterovirus 71 2A protease.
ACS Bio. & Med. Chem. AU. 2, 4, 437–449 (2022).


Yuan, H.S*.
短命的RNA — 切與不切之間
NSRRC News Letter, 117, 3-5 (2021).

Agrawal, S., Jain, M., Yang, W.-Z. and Yuan*, H. S.
Frontotemporal dementia-linked P112H mutation of TDP-43 induces protein structural change and impairs its RNA binding function.
Prot. Sci. 30, 350-365 (2021).

Golzarroshan, B., Jain, M. and Yuan*, H. S.
RNA-binding proteins in bacterial and mitochondrial RNA decay.
In: Jez Joseph (eds.) Encyclopedia of Biological Chemistry, 3rd Edition.
vol. 3, pp. 517–526 (2021).

Chen, T., Fei, C.-Y., Chen, Y. P., Sargsyan, K., Chang, C.-P., Liang, J.J., Liao, C.-C., Lin, Y.-L., Yuan*, H. S. and Lim*, C.
Synergistic inhibition of SARS-CoV-2 replication using disulfiram/ebselen and remdesivir.
ACS Pharmacol. Transl. Sci. 4, 898-907 (2021).


Wu&, C.C., Lin&, J.L.J. and Yuan*, H. S. 
Structures, mechanisms and functions of His-Me finger nucleases. 
Trends Biochem. Sci. 45, 935-946 (2020).

Sargsyan&, K., Lin&, C.C., Chen&, T., Grauffel, C., Chen, Y.P., Yang, W.-Z., Liang, J.J., Liao, C.-C., Lin, Y.-L., Yuan*, H. S. and Lim*, C.
Multi-targeting of functional cysteines in multiple conserved SARS-CoV-2 domains by clinically safe Zn-ejectors.
Chem. Sci. 11, 9904-9909 (2020).

Lin, C.-C., Chen, Y. P., Yang, W. Z., Shen, J.C.K., and Yuan*, H. S.
Structural insights into CpG-specific DNA methylation by human DNA methyltransferase 3B 
Nucleic Acids Res. 48, 3949-3961 (2020).


Wu, C.C., Lin, J.L.J., Yang-Yen, H.-F. and Yuan*, H. S.  
A unique exonuclease ExoG cleaves at the junction between RNA and DNA in mitochondrial DNA replication.  
Nucleic Acids Res. 47, 5405-5419 (2019).

Chu, L.-Y., Agrawal, S., Chen, Y. P., Yang, W. -Z. and Yuan*, H. S. 
Structural insights into nanoRNA degradation by human Rexo2
RNA 25, 737-746 (2019).

Agrawal, S., Kuo, P.-H., Chu, L.-Y., Golzarroshan, B., Jain, M. and Yuan*, H. S. 
RNA recognition motifs of disease-linked RNA-binding proteins contribute to amyloid formation.  
Sci. Rep. 9, 6171 (2019).


Golzarroshan, B., Lin, C.-L., Li, C.-L., W.-Z. Yang, Chu, L.-Y., Agrawal, S. and Yuan*, H. S.
Crystal structure of dimeric human PNPase reveals why disease-linked mutants suffer from low RNA import and degradation activities. 
Nucleic Acids Res. 
46, 8630-8640 (2018).

Li, C.-L., W.-Z. Yang, Shi, Z. and Yuan*, H. S. 
Tudor staphylococcal nuclease is a structure-specific ribonuclease that degrades RNA at unstructured regions during microRNA decay.
 24, 739-748 (2018).


Chu, L.-Y., Hsieh, T.-J., Golzarroshan, B., Chen, Y.-P., Agrawal, S. and Yuan*, H. S.
Structural insights into RNase R in RNA unwinding and degradation. 
Nucleic Acids Res. 45,12015–12024(2017)

Huen, J., Lin, C.-L., Yi, W.-L., W.-Z. Yang, Golzarroshan, B. and Yuan*, H. S.
Structural insights into a unique dimeric DEAD-box helicase CshA that promotes RNA decay. 
Structure 25, 469–481 (2017).


Lin, J. L. J., Wu, C.-C., Yang, W.-Z. and and Yuan*, H. S. 
Crystal structure of endonuclease G in complex with DNA reveals how it nonspecifically degrades DNA as a homodimer.
Nucleic Acids Res. 44,10480-10490 (2016).

Huang, K.-W., Hsu, K.-C., Chu, L.-Y., Yang, J.-M. Yuan*, H. S. and Hsiao*, Y.-Y. 
Identification of inhibitors for the DEDDh family of exonucleases and a unique inhibition mechanism revealed by crystal structure analysis of CRN-4 bound with 2-morpholin-4-ylethanesulfonate (MES). 
J. Med. Chem. 59(17):8019-29 (2016).

Lin, J. L. J., Nakagawa, A., Skeen-Gaar, R. Yang, W.-Z., X., Ge, S., Mitani, Xue*, D. and Yuan*, H. S. 
Oxidative stress impairs cell death by repressing the nuclease activity of Endonuclease G. 
Cell Rep.12, 279-287 (2016).

Zhou, Q., Li, H., Li, H., Nakagawa, A., Lin, J. L. J., Lee, E.-S., Harry, B.L., Skleen-Gaar, R., Shehiro, Y., William, D., Mitani, S., Yuan, H. S., Kang*, B.-H., Xue*, D. 
Mitochondrial endonuclease G mediates breakdown of paternal mitochondria upon fertilization. 
353, 394-399 (2016).

Lee, Y.-M., Duh, Y., Wang, S.-T., Lai*, M.M.C., Yuan*, H. S. and Lim*, C.
Using an old drug to target a new drug site: Application of disulfiram to target the Zn-site in HCV NS5A protein.
J. Am. Chem. Soc. 138, 3856-62 (2016).

Chiang, C. -H., Grauffel, C. Wu, L.-S., Kuo, P.-H., Doudeva, L. G, Lim, C., Shen, C.K.J. and Yuan*, H. S.
Structural analysis of disease-related TDP-43 D169G mutation: linking enhanced stability and caspase cleavage efficiency to protein accumulation.

Sci. Rep. 6: 21581 (2016).


Duh, Y., Hsiao, Y.-Y., Li, C.-L., Huang, J. C. and  Yuan*, H. S. 
Aromatic residues in RNase T stack with nucleobases to guide  the sequence-specific recognition and cleavage of nucleic acids.
Protein Sci. 24, 1934-1941 (2015).


Hsiao, Y.-Y., Fang, W.-H., Lee, C.-C, Chen, Y.-P., Hsu, P.-C. and Yuan*, H. S.  
Structural insights into DNA repair by RNase T, an exonuclease processing 3′ end of structured DNA in repair pathways. 
PLoS Biol. 12, 3, e1001803 (2014).

Kuo, P.-H, Chiang, C.-H, Wang, Y.-T., Doudeva, L. G., and Yuan*, H. S.  
The crystal structure of TDP-43 RRM1-DNA complex reveals the specific recognition for UG- and TG-rich nucleic acids. 
Nucleic Acids Res. 42, 4712-4722 (2014).

Chen, Y.-J., Li, C.-L., Hsiao, Y.-Y., Duh, Y. and Yuan*, H. S.
Structure and function of TatD exonuclease in DNA repair. 
Nucleic Acids Res.10776-10785 (2014).

Fang, Y.-S., Chang, Y.-J., Kuo, P.-H., Tsai, K.-J., Liao, J.Y., Chou, S,-C, Lin V., Yuan, H. S., Cheng, I. H, Tu, P.-H., and Chen*,Y.-R.
Full-length TDP-43 forms toxic amyloid oligomers that are present in frontotemporal lobar dementia-TDP patients. 
Nature Comm., 5, 4824 (2014).


Lee, Y.-M., Wang, Y.-T., Duh, Y., Yuan*, H. S. and Lim*, C.  
Identification of labile Zn sites in drug-target proteins.
J. Am. Chem. Soc. 2013, 135, 4028-4031 (2013).  

Wang, Y. -T., Kuo, P. -H., Chiang, C. -H, Liang., J -R., Chen, Y. -R., Wang, S., Shen, J.C.K., and Yuan*, H. S.
The truncated C-terminal RNA recognition motif of TDP-43 protein plays a key role in forming proteinaceous aggregates.
J. Biol. Chem. 2013, 288, 13, 9049–9057 (2013). 


Su. M. W., Yuan, S. H. and W. C. Chu* 
Recombination in the non-structural gene region in type-2 dengue viruses. 
Intervirol. 2012, 55, 225-230 (2012).

Hsiao, Y.-Y., Duh, Y., Chen, Y.-P., Wang, Y.-T., and Yuan*, H. S. 
How an exonuclease decides where to stop in trimming of nucleic acids: crystal structures of RNase T-product complexes. 
Nucleic Acids Res. 40, 8144-8154 (2012).

Lin, J. L. J., Lin, C. L., Hsiao, Y. Y., Doudeva, L. G., Yang, W.-Z., Wang, Y.-T. and Yuan*, H. S. 
Structural insights into DNA binding and cleavage by CED-3 Protease Suppressor-6 (CPS-6) from Caenorhabditis elegans.
J. Biol. Chem. 287, 10, 7110-7120 (2012).
Lin C. L., Wang, Y.-T, Hsiao, Y.-Y., Yang, W.-Z. and Yuan*, H. S.  
Crystal structure of human polynucleotide phosphorylase: Insights into its domain function in RNA binding and degradation. 
Nucleic Acids Res. 40, 4146-4157(2012).


Hsiao, Y.-Y., Yang, C.-C, Lin C. L., Lin, J. L. J., Duh, Y. and Yuan*, H. S. 

Structural basis for RNA trimming by RNase T in stable RNA 3'-end maturation.
Nature Chem. Biol. 7, 236-243(2012).


Yang, C.-C, Wang, Y.-T., Hsiao, Y. Y., Doudeva, L. G., Kuo, P.-H., Chow, S. Y. and Yuan*, H. S. 
Structural and biochemical characterization of CRN-5 and Rrp46: an exosome component participating in apoptotic DNA degradation.
RNA 16: 1748-1759 (2010). 

Fu, C. C., Lin, C. F., Gao, Q. Z., Yang, W. Z., Lim, T. S., Yang, L. L, Yen, C. F., Chang, W. H., Yuan, H. S., Sheu*, S. Y., Yang*, D. Y., Fann, W.  
Fis-protein induces rod-like DNA bending. 
Chem. Phys. Letter 500, 318-322 (2010).


Su, M.-W., Lin, H.-M., Yuan*, H. S. and Chu*, W.-C
Categorizing host-dependent RNA viruses by principal component analysis of their coden usage preferences.
J. Comp. Biol. 16, 1539-1547 (2009).

Wang, Y.-T., Wright, J, D., Doudeva, L. G., H -C., Lim*, C. and Yuan*, H. S. 
Redesign of high-affinity nonspecifid nucleases with altered sequence preference.
J. Am. Chem. Soc. 2009, 131, 17345-17353 (2009).

Hsiao, Y. Y., Nakagawa, A., Shi, Z., Mitani, S., Xue, D. and Yuan*, H. S. 
Crystal structure of CRN-4: implications for domain function in apoptotic DNA degradation. 
Mol. Cell. Biol. 29, 2, 448-457 (2009). 
Lin, Y.-S., Tsai; L.-C., Lee, S.-H., Yuan, H. S. and Shyur*, L.-F. 
Structural and catalytic roles of residues located in beta13 strand and the following beta-turn loop in Fibrobacter succinogenes 1,3-1,4- beta -D-glucanase. 
Biochim. Biophys. Acta. 1790, 231–239 (2009).

Kuo, P,-S, Doudeva, L. G., Wang, Y.-T., Shen, C.-K. J. and Yuan*, H. S. 
Structural insights into TDP-43 in nucleic acid binding and domain interactions. 
Nucleic Acids Res. 37, 6, 1799-1808 (2009).  


Shi, Z., Yang, W.-Z., Lin-Chao, S., Chak, K.-F. and Yuan*, H. S.  
Crystal structure of Escherichia coli PNPase: central channel residues are involved in processive RNA degradation.
RNA 14, 1-11 (2008).

Li, C. -L.,Yang, W. -Z., Chen, Y. -P. and Yuan*, H. S.
Structural and functional insights into human Tudor-SN, a key component linking RNA interference and editing. 
Nucleic Acid Res. 36, 11, 3579-3589 (2008). 
Lei, G. -S., Chen, C. -J., Yuan, H. S., Wang., S. -H. and Hu*, S. -T. 
Inhibition of IS2 transposition by factor for inversion stimulation.  
FEMS Microbiol Lett. 275, 98-105 (2007). 
Huang, H. and Yuan*, H. S.   
The conserved asparagine in the HNH motif plays an important structural role in metal finger endonucleases.   
J. Mol. Biol. 368, 3, 812-821 (2007). 
Wang, Y. -T., Yang, Y. -J., Li, C. -L., Doudeva, L. G., and Yuan*, H. S. 
Structural basis for sequence-dependent DNA cleavage by nonspecific endonucleases. 
Nucleic Acid Res. 35, 2, 584-594 (2007).
Pan, Y. -H., Liao, C. -C., Kuo, C. -C., Duan, K.-J., Liang, P.-H, Yuan, H. S., Hu, S.-T. and Chak*, K.-F.  
The critical roles of polyamines in regulating ColE7 production and restricting ColE7 uptake of the colicin-producing Escherichia coli. 
J. Biol. Chem.  281, 13083 (2006).
Doudeva, L. G., Huang, H., Hsia, K.-C., Shi, Z., Li, C. -L., Cheng, Y. -S. and Yuan*, H. S. 
Crystal structural analysis and metal-dependent stability and activity studies of the ColE7 endonuclease domain in complex with DNA/Zn2+ or inhibitor/Ni2+. 
Protein Sci. 15, 269-280 (2006).
Cheng, Y.-S., Shi, Z., Doudeva, L. G., Yang, W. -Z., Chak, K. -F. and Yuan*, H. S. 
High-resolution crystal structure of a truncated ColE7 translocation domain: Implications for colicin transport across membranes.  
J. Mol. Biol. 356, 22-31 (2006).
Hsia, K.-C., Li, C. -L. and Yuan*, H. S. 
Structural and functional insight into the sugar-nonspecific nucleases in host defense. 
Curr. Opin. Struct. Biol. 15, 126-134 (2005).

Liu, H., Peng, H.-W., Cheng, Y.-S., Yuan, H. S. and Yang-Yen*, H.-F. 
Stabilization and enhancement of the antiapoptotic activity of Mcl-1 by TCTP.  
Mol. Cell. Biol. 3117–3126 (2005).
Shi, Z., Chak. K.-F. and Yuan*, H. S. 
Identification of an essential cleavage site in ColE7 required for import and killing of cells.  
J. Biol. Chem. 2005, 280, 24663-24668 (2005).
Hsia, K.-C., Chak, K.-F., Liang, P. -H., Cheng, Y. -S., Ku, W. -Y. and Yuan*, H. S.  
DNA binding and degradation by the H-N-H protein ColE7 
Structure 12, 205-214 (2004). 
Lin, Y.-H., Liao, C. -C., Liang, P. -H., Yuan*, H. S. and Chak*, K. -F. 
Involvement of colicin in the limited protection of the colicin producing cells against bacteriophage 
Biochem. Biophys. Res. Commun. 318, 81-87 (2004). 
Tsai, L. -C., Shyur, L. -F., Lee, S. -H., Lin, S. -S. and Yuan*, H. S.  
Crystal structure of a natural circularly-permutated jellyroll protein: 1,3-1,4-beta-D-glucanase from Fibrobacter succinogenes. 
J. Mol. Biol. 330, 607-620 (2003). 
Li, C. -L., Hor, L. -I., Chang, Z. -F., Tsai, L. -C., Yang, W. -Z. and Yuan*, H. S.  
DNA binding and cleavage by the periplasmic nuclease Vvn- A novel structure with a known active site. 
EMBO J. 22, 4014-4025 (2003). 
Chang, S. -J., Hsieh, S. -Y., Yuan, H. S. and Chak*, K.-F.  
Characterization of the specific cleavage of ceiE7-mRNA of the bactericidal ColE7 operon. 
Biochem. Biophys. Res. Commun. 299, 613-620 (2002). 

Cheng, Y. -S., Hsia, K. -C., Doudeva, L. G., Kin-Fu Chak and Yuan*, H. S. 
The crystal structure of the nuclease domain of colicin E7 suggests a mechanism for binding to double-stranded DNA by the H-N-H endonucleases. 
J. Mol. Biol. 324, 227-236 (2002). 
Sui, M. -J., Tsai, L. -C., Hsia, K. -C., Doudeva, L. G., Ku, W.-Y., Han, G. W. and Yuan*, H. S. 
Metal ions and phosphate binding in the H-N-H motif: Crystal structures of the nuclease domain of ColE7/Im7 in complex with a phosphate ion and different divalent metal ions.  
Protein Sci. 11, 2947-2957 (2002). 
Cheng, H. -L., Tsai, L. -C., Lin, S. -S., Yuan*, H. S., Yang, N. -S., Lee, S. -H. and Shyur*, L. -F. 
Mutagenesis of Trp54 and Trp203 residues on Fibrobacter Succinogens 1,3-1,4-b-D-glucanase significantly affects catalytic activities of the enzyme.  
Biochemistry 2002, 41, 8759-8766 
Ku, W. -Y., Liu, Y. -W., Hsu, Y. -C., Liao, C. -C., Liang, P. -H., Yuan, H. S. and Chak*, K. -F.  
The zinc ion in the HNH motif of the endonuclease domain of colicin E7 is not required for DNA binding but is essential for DNA hydrolysis. 
Nucleic Acid Res. 30, 1670-1678 (2002).
Yang Z., Zhang H., Hung, H. -C., Kuo, C. -C., Tsai, L. -C., Yuan, H. S., Chou, W. -Y., Chang, G. -G., Tong*, L.  
Structural studies of the pigeon cytosolic NADP(+)-dependent malic enzyme.  
Protein Sci. 11:332-41 (2002). 


Chen, J. L., Tsai, L. C., Wen, T. N., Tang, J. B., Yuan*, H. S. and Shyur*, L. F.
Directed mutagenesis of specific active site residues on Fibrobacter succinogenes 1,3-1,4-beta-D-glucanase significantly affects catalysis and enzyme structural stability. 
J. Biol. Chem. 276, 17895-17901 (2001). 

Tsai, L. C., Shyur, L. F., Lin, S. S., Yuan*, H. S. 
Crystallization and preliminary X-ray diffraction analysis of the 1,3-1,4-beta-D-glucanase from Fibrobacter succinogenes. 
Acta Cryst. D. 57, 1303-1306 (2001). 
Cheng, Y.-S., Yang, W.-Z., Johnson, R. C. and Yuan*, H. S. 
Structure analysis of the transcriptional activation region on Fis: Crystal structures of Six Fis Mutants with Different activation properties.   
J. Mol. Biol. 302, 1139-1151 (2000). 

Ko, T.-P., Liao, C.-C., Ku, W.-Y., Chak, K.-F. and Yuan*, H. S. 
The crystal structure of the DNase domain of colicin E7 in complex with its inhibitor Im7 protein. 
Structure 7, 91-102 (1999). 
Tsai, L.-C, Kuo, C.-C., Chou, W.-Y., Chang, G.-G. and Yuan*, H. S. 
Crystallization and preliminary x-ray diffraction analysis of malic enzyme from pigeon liver. 
Acta Cryst. D. 55, 1930-1932 (1999). 
Ko, T.-P., Yang, W.-Z, Wu, S.-P., Hsin, T., and Yuan*, H. S. 
The preliminary crystallographic analysis of the open-form E. coli tyrosine aminotransfer ase bound with a cofactor pyridoxal 5'-phosphate. 
Acta Cryst. D. 55, 1474-1477 (1999).  
Lu, F.-M., Yuan*, H. S., Hsu, Y.-C., Chang, S.-J., Chak*, K.-F.  
Hierarchical order of critical residues on the immunity-determining region of the Im7 protein which confer specific immunity to its cognate colicin. 
Biochem. Biophys. Res. Commun. 264, 69-75 (1999). 
Chang*, S.-L., Chao, C.-H., Huang, Y.-S., Jean, Y.-C., Sheu, H.-S., Liang, F.-J., Chen, C.-K., Yuan*, H. S. 
Quantitative phase determination for macromolecular crystals using stereoscopic multibeam imaging 
Acta. Cryst. A. 55, 933-938 (1999).  
Hsu, W.-H., Chien, F.-T., Hsu, C.-L., Wang, T.-C., Yuan*, H. S., and Wang*, W.-C. 
Expression, crystallization and preliminary x-ray diffraction studies of N- carbamyl-D-amino-acid amidohydrolase from Agrobacterium radiobacter. 
Acta. Cryst. D. 55, 694-695 (1999).  
Yang, W.-Z, Ko, T. P., Corselli, L., Johnson, R. C. and Yuan*, H. S. 
The conversion from a beta-strand to an alph-helix induced by a single-site mutation identified in the crystal structures of Fis mutant Pro26Ala. 
Protein Sci. 7, 1875-1883 (1998). 
Safo, M. K., Yang, W.-Z., Corselli, L., Crampton, S., Yuan*, H. S, and Johnson*, R. C. 
The transactivation region of the Fis protein that controls site-specific DNA inversion contains extended mobile beta-hairpin arms. 
EMBO J. 16, 6860-6873 (1997). 
Hsieh, S. -H., Ko, T. -P., Tseng, M. -Y., Ku, W. -Y., Chak*, K.-F, and Yuan*, H. S. 
A novel role of ImmE7 in the autoregulatory expression of ColE7 operon and identification of possible ribonuclease active sites in the crystal structure of dimeric ImmE7. 
EMBO J. 16, 1444-1454 (1997). 

Chak, K.-F., Safo, M. K., Ku, W.-Y., Hsieh, S.-Y., and Yuan*, H. S. 
The crystal structure of the ImmE7 protein suggests a possible colicin-interacting surface. 
Proc. Natl. Acad. Sci. USA 93, 6437-6442 (1996). 

Ku, W. -Y., Wang, C. -S., Chen, J. -Y., Chak, K.-F., Safo, M. K. and Yuan*, H. S. 
Crystallization and preliminary crystallographic analysis of ImmE7 protein of Colicin E7. 
Proteins, Struc. Func. & Genet. 23, 588-590 (1995).
Yuan*, H. S., Yang, W.-Z., Wang, S. S., Finkel, S. E. and Johnson, R. C. 
The structure of Fis mutant Pro61-Ala illustrates that the kink within the long a-helix is not due to the presence of the proline residue.  
J. Biol. Chem. 269, 46, 28947-28954 (1994).
Yuan*, H. S., Stevens, R. C., Kotzle, T. F. and Bau*, R. 
Determination of the absolute configuration of (S)-(+)-neopentyl-1-d alcohol by neutron diffraction study of strychnium neopentylphthalate. 
Proc. Natl. Acad. Sci. USA 91, 12872-12876 (1994).

IMB Academia Sinica