Identification of probable genomic packaging signal sequence from SARS-CoV genome by bioinformatics analysis.
OBJECTIVE
To predict the probable genomic packaging signal of SARS-CoV by bioinformatics analysis. The derived packaging signal may be used to design antisense RNA and RNA interfere (RNAi) drugs treating SARS.


METHODS
Based on the studies about the genomic packaging signals of MHV and BCoV, especially the information about primary and secondary structures, the putative genomic packaging signal of SARS-CoV were analyzed by using bioinformatic tools. Multi-alignment for the genomic sequences was performed among SARS-CoV, MHV, BCoV, PEDV and HCoV 229E. Secondary structures of RNA sequences were also predicted for the identification of the possible genomic packaging signals. Meanwhile, the N and M proteins of all five viruses were analyzed to study the evolutionary relationship with genomic packaging signals.


RESULTS
The putative genomic packaging signal of SARS-CoV locates at the 3' end of ORF1b near that of MHV and BCoV, where is the most variable region of this gene. The RNA secondary structure of SARS-CoV genomic packaging signal is very similar to that of MHV and BCoV. The same result was also obtained in studying the genomic packaging signals of PEDV and HCoV 229E. Further more, the genomic sequence multi-alignment indicated that the locations of packaging signals of SARS-CoV, PEDV, and HCoV overlaped each other. It seems that the mutation rate of packaging signal sequences is much higher than the N protein, while only subtle variations for the M protein.


CONCLUSIONS
The probable genomic packaging signal of SARS-CoV is analogous to that of MHV and BCoV, with the corresponding secondary RNA structure locating at the similar region of ORF1b. The positions where genomic packaging signals exist have suffered rounds of mutations, which may influence the primary structures of the N and M proteins consequently.
Qin
Lei
L
Shanghai Center for Bioinformation Technology, Shanghai 201203, China.
Xiong
Bin
B
Luo
Cheng
C
Guo
Zong-Ming
ZM
Hao
Pei
P
Su
Jiong
J
Nan
Peng
P
Feng
Ying
Y
Shi
Yi-Xiang
YX
Yu
Xiao-Jing
XJ
Luo
Xiao-Min
XM
Chen
Kai-Xian
KX
Shen
Xu
X
Shen
Jian-Hua
JH
Zou
Jian-Ping
JP
Zhao
Guo-Ping
GP
Shi
Tie-Liu
TL
He
Wei-Zhong
WZ
Zhong
Yang
Y
Jiang
Hua-Liang
HL
Li
Yi-Xue
YX
D000595:Amino Acid Sequence; D001483:Base Sequence; D019295:Computational Biology; D028941:Coronavirus 229E, Human / Q000235:genetics; D017938:Coronavirus, Bovine / Q000235:genetics; D016679:Genome, Viral; D006801:Humans; D008969:Molecular Sequence Data; D006517:Murine hepatitis virus / Q000235:genetics; D019590:Nucleocapsid Proteins / Q000235:genetics*; D021382:Protein Sorting Signals / Q000235:genetics*; D017433:Protein Structure, Secondary; D034622:RNA Interference; D016372:RNA, Antisense / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics* / Q000302:isolation & purification; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D045169:Severe Acute Respiratory Syndrome / Q000821:virology*; D014763:Viral Matrix Proteins / Q000235:genetics*
D019590:Nucleocapsid Proteins; D021382:Protein Sorting Signals; D016372:RNA, Antisense; D012367:RNA, Viral; D014763:Viral Matrix Proteins