Trimethylguanosine capping selectively promotes expression of Rev-dependent HIV-1 RNAs

Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14787-92. doi: 10.1073/pnas.1009490107. Epub 2010 Aug 2.


5'-mRNA capping is an early modification that affects pre-mRNA synthesis/splicing, RNA cytoplasmic transport, and mRNA translation and turnover. In eukaryotes, a 7-methylguanosine (m7G) cap is added to newly transcribed RNA polymerase II (RNAP II) transcripts. A subset of RNAP II-transcribed cellular RNAs, including small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), and telomerase RNA, is further hypermethylated at the exocyclic N2 of the guanosine to create a trimethylguanosine (TMG)-capped RNA. Some of these TMG-capped RNAs are transported within the nucleus and from the nucleus to the cytoplasm by the CRM-1 (required for chromosome region maintenance) protein. CRM-1 is also used to export Rev/RRE-dependent unspliced/ partially spliced HIV-1 RNAs. Here we report that like snRNAs and snoRNAs, some Rev/RRE-dependent HIV-1 RNAs are TMG-capped. The methyltransferase responsible for TMG modification of HIV-1 RNAs is the human PIMT (peroxisome proliferator-activated receptor-interacting protein with methyltransferase) protein. TMG capping of unspliced/partially spliced HIV-1 RNAs represents a new regulatory mechanism for selective expression.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Binding Sites / genetics
  • Blotting, Western
  • Gene Expression Regulation, Viral
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Guanosine / analogs & derivatives*
  • Guanosine / metabolism
  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • HeLa Cells
  • Humans
  • Microscopy, Confocal
  • Mutation
  • Protein D-Aspartate-L-Isoaspartate Methyltransferase / genetics
  • Protein D-Aspartate-L-Isoaspartate Methyltransferase / metabolism
  • RNA / genetics
  • RNA / metabolism
  • RNA Caps / metabolism
  • RNA Processing, Post-Transcriptional
  • RNA, Viral / genetics*
  • RNA, Viral / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Telomerase / genetics
  • Telomerase / metabolism
  • Transfection
  • Virus Replication / drug effects
  • rev Gene Products, Human Immunodeficiency Virus / genetics*
  • rev Gene Products, Human Immunodeficiency Virus / metabolism


  • RNA Caps
  • RNA, Viral
  • rev Gene Products, Human Immunodeficiency Virus
  • telomerase RNA
  • Guanosine
  • Green Fluorescent Proteins
  • 7-methylguanosine
  • RNA
  • PCMT1 protein, human
  • Protein D-Aspartate-L-Isoaspartate Methyltransferase
  • Telomerase