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Posttranscriptional regulation of retroviral gene expression: primary RNA transcripts play three roles as pre‐ mRNA , mRNA , and genomic RNA
Author(s) -
LeBlanc Jason,
Weil Jason,
Beemon Karen
Publication year - 2013
Publication title -
wiley interdisciplinary reviews: rna
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.225
H-Index - 71
eISSN - 1757-7012
pISSN - 1757-7004
DOI - 10.1002/wrna.1179
Subject(s) - rna , biology , rna splicing , rna editing , rna silencing , gene expression , intron , transcription (linguistics) , polyadenylation , microbiology and biotechnology , messenger rna , post transcriptional modification , gene , genetics , rna interference , linguistics , philosophy
After reverse transcription of the retroviral RNA genome and integration of the DNA provirus into the host genome, host machinery is used for viral gene expression along with viral proteins and RNA regulatory elements. Here, we discuss co‐transcriptional and posttranscriptional regulation of retroviral gene expression, comparing simple and complex retroviruses. Cellular RNA polymerase II synthesizes full‐length viral primary RNA transcripts that are capped and polyadenylated. All retroviruses generate a singly spliced env mRNA from this primary transcript, which encodes the viral glycoproteins. In addition, complex viral RNAs are alternatively spliced to generate accessory proteins, such as Rev, which is involved in posttranscriptional regulation of HIV ‐1 RNA . Importantly, the splicing of all retroviruses is incomplete; they must maintain and export a fraction of their primary RNA transcripts. This unspliced RNA functions both as the major mRNA for Gag and Pol proteins and as the packaged genomic RNA . Different retroviruses export their unspliced viral RNA from the nucleus to the cytoplasm by either Tap‐dependent or Rev/ CRM1 ‐dependent routes. Translation of the unspliced mRNA involves frame‐shifting or termination codon suppression so that the Gag proteins, which make up the capsid, are expressed more abundantly than the Pol proteins, which are the viral enzymes. After the viral polyproteins assemble into viral particles and bud from the cell membrane, a viral encoded protease cleaves them. Some retroviruses have evolved mechanisms to protect their unspliced RNA from decay by nonsense‐mediated RNA decay and to prevent genome editing by the cellular APOBEC deaminases. WIREs RNA 2013, 4:567–580. doi: 10.1002/wrna.1179 This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing RNA Export and Localization > Nuclear Export/Import RNA Turnover and Surveillance > Regulation of RNA Stability RNA in Disease and Development > RNA in Disease