The Herpesvirus saimiri small nuclear RNAs recruit AU-rich element-binding proteins but do not alter host AU-rich element-containing mRNA levels in virally transformed T cells

Mol Cell Biol. 2004 May;24(10):4522-33. doi: 10.1128/mcb.24.10.4522-4533.2004.

Abstract

Herpesvirus saimiri (HVS) encodes seven Sm-class small nuclear RNAs, called HSURs (for Herpesvirus saimiri U RNAs), that are abundantly expressed in HVS-transformed, latently infected marmoset T cells but are of unknown function. HSURs 1, 2, and 5 have highly conserved 5'-end sequences containing the AUUUA pentamer characteristic of AU-rich elements (AREs) that regulate the stability of many host mRNAs, including those encoding most proto-oncogenes and cytokines. To test whether the ARE-containing HSURs act to sequester host proteins that regulate the decay of these mRNAs, we demonstrate their in vivo interaction with the ARE-binding proteins hnRNP D and HuR in HVS-transformed T cells using a new cross-linking assay. Comprehensive Northern and microarray analyses revealed, however, that the levels of endogenous ARE-containing mRNAs are not altered in T cells latently infected with HVS mutants lacking HSURs 1 and 2. HSUR 1 binds the destabilizing ARE-binding protein tristetraprolin induced following activation of HVS-transformed T cells, but even in such stimulated cells, the levels of host ARE-containing mRNAs are not altered by deletion of HSURs 1 and 2. Instead, HSUR 1 itself is degraded by an ARE-dependent pathway in HVS-transformed T cells, suggesting that HVS may take advantage of the host ARE-mediated mRNA decay pathway to regulate HSUR expression. This is the first example of posttranscriptional regulation of the expression of an Sm small nuclear RNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Surface / metabolism
  • Base Composition
  • Base Sequence
  • Callithrix
  • Cell Line
  • Cell Transformation, Viral
  • ELAV Proteins
  • ELAV-Like Protein 1
  • Herpesvirus 2, Saimiriine / genetics*
  • Herpesvirus 2, Saimiriine / metabolism*
  • Heterogeneous-Nuclear Ribonucleoprotein D / metabolism
  • In Vitro Techniques
  • Molecular Sequence Data
  • Mutation
  • Nucleic Acid Conformation
  • Protein Binding
  • RNA, Messenger / metabolism*
  • RNA, Small Nuclear / chemistry
  • RNA, Small Nuclear / genetics*
  • RNA, Small Nuclear / metabolism*
  • RNA, Viral / chemistry
  • RNA, Viral / genetics*
  • RNA, Viral / metabolism*
  • RNA-Binding Proteins / metabolism
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / virology*

Substances

  • Antigens, Surface
  • ELAV Proteins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • Heterogeneous-Nuclear Ribonucleoprotein D
  • RNA, Messenger
  • RNA, Small Nuclear
  • RNA, Viral
  • RNA-Binding Proteins