Mining the human complexome database identifies RBM14 as an XPO1-associated protein involved in HIV-1 rev function

Sona Budhiraja, Hongbing Liu, Jacob Couturier, Anna Malovannaya, Jun Qin, Dorothy E. Lewis, Andrew P. Rice

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

By recruiting the host protein XPO1 (CRM1), the HIV-1 Rev protein mediates the nuclear export of incompletely spliced viral transcripts. We mined data from the recently described human nuclear complexome to identify a host protein, RBM14, which associates with XPO1 and Rev and is involved in Rev function. Using a Rev-dependent p24 reporter plasmid, we found that RBM14 depletion decreased Rev activity and Rev-mediated enhancement of the cytoplasmic levels of unspliced viral transcripts. RBM14 depletion also reduced p24 expression during viral infection, indicating that RBM14 is limiting for Rev function. RBM14 has previously been shown to localize to nuclear paraspeckles, a structure implicated in retaining unspliced HIV-1 transcripts for either Rev-mediated nuclear export or degradation. We found that depletion of NEAT1 RNA, a long noncoding RNA required for paraspeckle integrity, abolished the ability of overexpressed RBM14 to enhance Rev function, indicating the dependence of RBM14 function on paraspeckle integrity. Our study extends the known host cell interactome of Rev and XPO1 and further substantiates a critical role for paraspeckles in the mechanism of action of Rev. Our study also validates the nuclear complexome as a database from which viral cofactors can be mined.

Original languageEnglish (US)
Pages (from-to)3557-3567
Number of pages11
JournalJournal of virology
Volume89
Issue number7
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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