Anomalous HIV-1 RNA, How Cap-Methylation Segregates Viral Transcripts by Form and Function

Kathleen Boris-Lawrie, Gatikrushna Singh, Patrick S. Osmer, Dora Zucko, Seth Staller, Xiao Heng

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

The acquisition of m7 G-cap-binding proteins is now recognized as a major variable driving the form and function of host RNAs. This manuscript compares the 5-cap-RNA binding proteins that engage HIV-1 precursor RNAs, host mRNAs, small nuclear (sn)-and small nucleolar (sno) RNAs and sort into disparate RNA-fate pathways. Before completion of the transcription cycle, the transcription start site of nascent class II RNAs is appended to a non-templated guanosine that is methylated (m7 G-cap) and bound by hetero-dimeric CBP80-CBP20 cap binding complex (CBC). The CBC is a nexus for the co-transcriptional processing of precursor RNAs to mRNAs and the snRNA and snoRNA of spliceosomal and ribosomal ribonucleoproteins (RNPs). Just as sn/sno-RNAs experience hyper-methylation of m7 G-cap to trimethylguanosine (TMG)-cap, so do select HIV RNAs and an emerging cohort of mRNAs. TMG-cap is blocked from Watson:Crick base pairing and disqualified from participating in secondary structure. The HIV TMG-cap has been shown to license select viral transcripts for specialized cap-dependent translation initiation without eIF4E that is dependent upon CBP80/NCBP3. The exceptional activity of HIV precursor RNAs secures their access to maturation pathways of sn/snoRNAs, canonical and non-canonical host mRNAs in proper stoichiometry to execute the retroviral replication cycle.

Original languageEnglish (US)
Article number935
JournalViruses
Volume14
Issue number5
DOIs
StatePublished - May 2022

Bibliographical note

Funding Information:
National Institutes of Health R01AI150460 to X.H. and K.B.-L. and the Hanlon and Schmidt Fellowship, College of Veterinary Medicine, University of Minnesota–Twin Cities to D.Z.Acknowledgments: Figures were created with BioRender.com.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • NCBP3
  • RNA virus
  • epigenetic modification
  • internal ribosome entry
  • junD
  • ribosome scanning
  • specialized translation
  • trimethylguanosine (TMG) cap

PubMed: MeSH publication types

  • Journal Article
  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

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