The Appropriate Ratio of Retroviral Structural Proteins Is Activated by the Spleen Necrosis Virus Post-Transcriptional Control Element

Gatikrushna Singh, Deepali Singh, Nicole Placek, Stacey Hull, Radhakrishna Sura, Kathleen Boris-Lawrie

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Retroviruses are atypical RNA viruses and express all viral functions on a single viral transcript. By unknown means, retroviruses subvert the host RNA-based quality control mechanisms that repress the translation of incompletely processed RNA in order to encode virion structural proteins in an appropriate ratio. Herein, flow cytometry experiments of spleen necrosis virus (SNV) molecular clones in mammalian cells determined the native ratio between fluorescent capsid-gfp and envelope-dsRed fusion proteins and its deregulation by 5′-UTR mutations. Deletion of the 5′-terminal post-transcriptional control element (PCE) upregulated the spliced transcripts that encode envelope and downregulated the unspliced transcripts that encode capsid. Moreover, the appropriate ratio of SNV transcripts was dysregulated by RNA interference of the host splicing regulatory factor SFPQ/PSF. Northern analysis determined the splicing pattern and half-life of the spliced transcripts was significantly increased by PCE mutations. Ribosome profiles demonstrated that PCE activates the translation of the unspliced transcripts, but not the spliced transcripts to balance the expression of an appropriate ratio between capsid and envelope protein. In conclusion, the native ratio between SNV unspliced and spliced transcripts is regulated by SNV 5′-UTR sequences. Our results identify a molecular basis for retrovirus subversion of RNA-based gene regulation in hosts that involves SFPQ/PSF.

Original languageEnglish (US)
Title of host publicationBiomotors and their Nanobiotechnology Applications
PublisherCRC Press
Pages265-278
Number of pages14
ISBN (Electronic)9780429511943
ISBN (Print)9780367196134
DOIs
StatePublished - Jan 1 2023

Bibliographical note

Publisher Copyright:
© 2024 selection and editorial matter, Peixuan Guo and Aibing Wang; individual chapters, the contributors.

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