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ISSN 1672-9145                                                Acta Biochim Biophys Sin 2005, 37(3): 210–214                                                   CN 31-1940/Q


In Vitro Construction of Effective M1GS Ribozymes Targeting HCMV UL54 RNA Segments

Yun-Zhen SU, Hong-Jian LI, Yue-Qin LI, Hao-Jun CHEN, Dong-Sheng TANG, Xin ZHANG, Hong JIANG, and Tian-Hong ZHOU*

 

College of Life Science and Technology, Jinan University, Guangzhou 510632, China

 

Abstract        Seven sequence-specific ribozymes (M1GS RNAs) derived in vitro from the catalytic RNA subunit of Escherichia coli RNase P and targeting the mRNAs transcribed by the UL54 gene encoding the DNA polymerase of human cytomegalovirus were screened from 11 ribozymes that were designed based on four rules: (1) the NCCA-3' terminal must be unpaired with the substrate; (2) the guide sequence (GS) must be at least 12 nt in length; (3) the eighth nucleotide must be U, counting from the site –1; and (4) around the cleavage site, the sites –1/+1/+2 must be U/G/C or C/G/C. Further investigation of the factors affecting the cleavage effect and the optimal ratio for M1GS/substrate was carried out. It was determined that the optimal ratio for M1GS/substrate was 2:1 and too much M1GS led to substrate degrading. As indicated above, several M1GS that cleaved HCMV UL54 RNA segments in vitro were successfully designed and constructed. Our studies support the use of ribozyme M1GS as antisense molecules to silence HCMV mRNA in vitro, and using the selection procedure as a general approach for the engineering of RNase P ribozymes.

 

Key words        ribonuclease P (RNase P); guide sequence; HCMV; DNA polymerase

 

 

 

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Received: November 9, 2004        Accepted: January 18, 2005

This work was supported by the grants from the National Natural Science Foundation of China (No. 30370776) and the Natural Science Foundation­ of Guangdong Province (36703, 021162 and 000718)

*Corresponding author: Tel, 86-20-85226386; E-mail, [email protected]