Differential Effects of Tra2ß Isoforms on HIV-1 RNA Processing and Expression

PLoS One. 2015 May 13;10(5):e0125315. doi: 10.1371/journal.pone.0125315. eCollection 2015.

Abstract

Balanced processing of HIV-1 RNA is critical to virus replication and is regulated by host factors. In this report, we demonstrate that overexpression of either Tra2α or Tra2β results in a marked reduction in HIV-1 Gag/Env expression, an effect associated with changes in HIV-1 RNA accumulation, altered viral splice site usage, and a block to export of HIV-1 genomic RNA. A natural isoform of Tra2β (Tra2ß3), lacking the N-terminal RS domain, also suppressed HIV-1 expression but had different effects on viral RNA processing. The functional differences between the Tra2β isoforms were also observed in the context of another RNA substrate indicating that these factors have distinct functions within the cell. Finally, we demonstrate that Tra2ß depletion results in a selective reduction in HIV-1 Env expression as well as an increase in multiply spliced viral RNA. Together, the findings indicate that Tra2α/β can play important roles in regulating HIV-1 RNA metabolism and expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation
  • HEK293 Cells
  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • HeLa Cells
  • Host-Pathogen Interactions
  • Humans
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA Splice Sites
  • RNA Splicing
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA, Viral / genetics*
  • RNA, Viral / metabolism
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Serine-Arginine Splicing Factors
  • Signal Transduction
  • Virus Replication
  • env Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors
  • env Gene Products, Human Immunodeficiency Virus / genetics*
  • env Gene Products, Human Immunodeficiency Virus / metabolism
  • gag Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors
  • gag Gene Products, Human Immunodeficiency Virus / genetics*
  • gag Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • Nerve Tissue Proteins
  • Protein Isoforms
  • RNA Splice Sites
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA, Viral
  • RNA-Binding Proteins
  • TRA2B protein, human
  • env Gene Products, Human Immunodeficiency Virus
  • gag Gene Products, Human Immunodeficiency Virus
  • Serine-Arginine Splicing Factors