HIV-1 mRNA 3' end processing is distinctively regulated by eIF3f, CDK11, and splice factor 9G8

Mol Cell. 2009 Oct 23;36(2):279-89. doi: 10.1016/j.molcel.2009.10.004.

Abstract

A genetic screen previously identified the N-terminal 91 amino acids of the eukaryotic initiation factor 3 subunit f (N91-eIF3f) as a potent inhibitor of HIV-1 replication. Overexpression of N91-eIF3f or full-length eIF3f reduced the level of HIV-1 mRNAs in the infected cell. Here we show that N91-eIF3f and eIF3f act by specifically blocking the 3' end processing of the HIV-1 pre-mRNA both in vivo and in vitro. Furthermore, the results suggest that eIF3f mediates this restriction of HIV-1 expression through the previously unsuspected involvement of a set of factors that includes eIF3f, the SR protein 9G8, and the cyclin-dependent kinase 11 (CDK11). eIF3f affects HIV-1 3' end processing by modulating the sequence-specific recognition of the HIV-1 pre-mRNA by 9G8.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cell Extracts
  • Cell Nucleus / metabolism
  • Cyclin-Dependent Kinases / metabolism*
  • Eukaryotic Initiation Factor-3 / chemistry
  • Eukaryotic Initiation Factor-3 / metabolism*
  • HIV Long Terminal Repeat / genetics
  • HIV-1 / genetics*
  • HIV-1 / physiology
  • HeLa Cells
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Nuclear Proteins
  • Nucleocytoplasmic Transport Proteins / metabolism*
  • Poly A / metabolism
  • Protein Binding
  • RNA 3' End Processing / genetics*
  • RNA, Messenger / metabolism
  • RNA, Viral / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Serine-Arginine Splicing Factors
  • Virus Replication

Substances

  • Cell Extracts
  • Eukaryotic Initiation Factor-3
  • Nuclear Proteins
  • Nucleocytoplasmic Transport Proteins
  • RNA, Messenger
  • RNA, Viral
  • RNA-Binding Proteins
  • Serine-Arginine Splicing Factors
  • Poly A
  • CDK11a protein, human
  • Cyclin-Dependent Kinases