Herpesvirus protein ICP27 switches PML isoform by altering mRNA splicing

Takayuki Nojima, Takako Oshiro-Ideue, Hiroto Nakanoya, Hidenobu Kawamura, Tomomi Morimoto, Yasushi Kawaguchi, Naoyuki Kataoka, Masatoshi Hagiwara

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Viruses use alternative splicing to produce a broad series of proteins from small genomes by utilizing the cellular splicing machinery. Since viruses use cellular RNA binding proteins for viral RNA processing, it is presumable that the splicing of cellular pre-mRNAs is affected by viral infection. Here, we showed that herpes simplex virus type 2 (HSV-2) modifies the expression of promyelocytic leukemia (PML) isoforms by altering pre-mRNA splicing. Using a newly developed virus-sensitive splicing reporter, we identified the viral protein ICP27 as an alternative splicing regulator of PML isoforms. ICP27 was found to bind preferentially to PML pre-mRNA and directly inhibit the removal of PML intron 7a in vitro. Moreover, we demonstrated that ICP27 functions as a splicing silencer at the 3′ splice site of the PML intron 7a. The switching of PML isoform from PML-II to PML-V as induced by ICP27 affected HSV-2 replication, suggesting that the viral protein modulates the splicing code of cellular pre-mRNA(s) governing virus propagation.

Original languageEnglish
Pages (from-to)6515-6527
Number of pages13
JournalNucleic acids research
Volume37
Issue number19
DOIs
Publication statusPublished - 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics

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