Degradation of Host MicroRNAs by Poxvirus Poly(A) Polymerase Reveals Terminal RNA Methylation as a Protective Antiviral Mechanism
Degradation of host microRNAs by poxvirus poly(A) polymerase reveals terminal RNA methylation as a protective antiviral mechanism
Backes, S. Shapiro, J. S. Sabin, L. R. Pham, A. M. Reyes, I. Moss, B. Cherry, S. tenOever, B. R.
Cell Host Microbe. 2012, 12(2): 200-210.
Speaker: Han Lee (李涵) Time: 14:00~15:00, Dec. 5, 2012
Commentator: Dr. Hsiao-Sheng Liu (劉校生老師) Place: Room 601
Abstract
The infections of several viruses involve small noncoding RNAs of host or virus which play an important role in post-transcriptional regulation. Small noncoding RNAs include microRNAs (miRNAs) which are generated from hairpin structure and function as post-transcriptional regulator, and small interfering RNAs (siRNAs) which are derived from long double-strand RNAs[1]. In general, miRNAs have little impact on the acute cellular response to virus infection but in contrast, there is significant interplay between miRNAs and chronic viral infections[2]. The authors asked why poxviruses, such as vaccinia virus (VACV), have not been reported to utilize the cellular miRNA pathway. These large, double-stranded DNA viruses transcribing genes could therefore benefit from the post-transcriptional regulation provided by miRNAs. But the apparent lack of encodedmiRNAs is not explained. The authors sequenced and analyzed the small RNAs from poxvirus-treated insect and mammalian cells. They discovered that VACV infection induced host-derived miRNAs specific polyadenylation and subsequent degradation, which are mediated by the virally encoded poly(A) polymerase. However, this activity was not observed on endogenous siRNAs (esiRNAs) that contain a 2’O-methyl group (2’OMe). In other words, miRNAs with this modification were also protected. VP55, a large subunit of VACV poly(A) polymerase, is both necessary and sufficient for miRNA polyadenylation and then destruction, this may offer an explanation that poxviruses, with large DNA genomes, do not encode and utilize miRNA to induce post-transcriptional silencing on target mRNA.
References
- Havens MA, Reich AA, Duelli DM, Hastings ML: Biogenesis of mammalian microRNAs by a non-canonical processing pathway. Nucleic acids research 2012, 40(10):4626-4640.
- Cullen BR: Viruses and microRNAs: RISCy interactions with serious consequences. Genes & development 2011, 25(18):1881-1894.