Journal
RNA BIOLOGY
Volume 17, Issue 6, Pages 816-827Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15476286.2020.1731664
Keywords
G-quadruplex; Alphaherpesvirinae; immediate early gene; 3MODIFIER LETTER PRIME-untranslated region; post-transcription regulation
Categories
Funding
- National Natural Science Foundation of China [31672558, 21732002, 31701791, 21502060, 31770191]
- Huazhong Agricultural University Scientific & Technological Self-innovation Foundation [2015RC013, 2662017PY113, 2662015PY208]
- Open fund of The State Key Laboratory of Bio-organic and Natural Products Chemistry, Chinese Academy of Sciences [SKLBNPC16343]
- Hubei Provincial Natural Science Foundation of China [2017CFB233]
- Fundamental Research Funds for the Central Universities [2662015QD046]
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RNA secondary structure elements in the mRNA 3MODIFIER LETTER PRIME-untranslated regions (3MODIFIER LETTER PRIMEUTR) 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 G(2)-quadruplex-forming sequence named PQS18-1 in the 3MODIFIER LETTER PRIMEUTR 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 G(3)-quadruplex mutant in the 3MODIFIER LETTER PRIMEUTR showed lower gene expression level than the wildtype G(2)-quadruplex. TMPyP4 destroyed PQS18-1 G(2)-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 G(2)-quadruplex in 3MODIFIER LETTER PRIMEUTR 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 G(2)-quadruplex in the 3MODIFIER LETTER PRIMEUTR of an immediate early gene of alphaherpesvirus and provides a new nucleic acid target for anti-virus drug design.
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