G2-quadruplex in the 3'UTR of IE180 regulates Pseudorabies virus replication by enhancing gene expression.
RNA secondary structure elements in the mRNA 3'-untranslated regions (3'UTR) play important roles in post-transcriptional regulation. RNA structure elements in the viral RNA provide valuable model for studying diverse regulation mechanisms. Herpesvirus genomes are double-stranded DNA with GC-rich sequences, which can be transcribed into abundant GC-rich RNAs. It is valuable to explore the structures and function of those GC-rich RNAs. We identified a G2-quadruplex-forming sequence named PQS18-1 in the 3'UTR of the unique immediate early gene of Pseudorabies virus (PRV), an important member of Alphaherpesvirinae subfamily. The RNA PQS18-1 was folded into parallel G-quadruplex structure, enhancing gene expression. Both non-G-quadruplex mutant and G3-quadruplex mutant in the 3'UTR showed lower gene expression level than the wildtype G2-quadruplex. TMPyP4 destroyed PQS18-1 G2-quadruplex and suppressed gene expression, accordingly reducing PRV replication by one titre in the PK15 cells at 24 h post infection. Our findings indicated that the RNA G2-quadruplex in 3'UTR was essential for high expression of IE180 gene, and it could be a specific post-transcription regulation element in response to small molecules or other macromolecules. This study discovers a novel RNA G2-quadruplex in the 3'UTR of an immediate early gene of alphaherpesvirus and provides a new nucleic acid target for anti-virus drug design.
['Zhang|Yashu|Y|', 'Liu|Sisi|S|0000-0002-6814-134X', 'Jiang|Hui|H|', 'Deng|Hui|H|', 'Dong|Chen|C|', 'Shen|Wei|W|', 'Chen|Haifeng|H|', 'Gao|Chao|C|', 'Xiao|Shaobo|S|', 'Liu|Zheng-Fei|ZF|', 'Wei|Dengguo|D|0000-0001-9923-789X']
D020413:3' Untranslated Regions D000818:Animals D001483:Base Sequence D054856:G-Quadruplexes D015967:Gene Expression Regulation, Viral D011558:Herpesvirus 1, Suid D017874:Immediate-Early Proteins D011557:Pseudorabies D014779:Virus Replication
post-transcription regulation immediate early gene Alphaherpesvirinae G-quadruplex 3ʹ-untranslated region