Cited by 86HIV Research and TreatmentRNA and protein synthesis mechanismsRNA Research and Splicing

RNA-guided assembly of Rev-RRE nuclear export complexes

Open access
Bai, Yun, Tambe, Akshay, Zhou, Kaihong, Doudna, Jennifer A·2014·eLife

Abstract

HIV replication requires nuclear export of unspliced and singly spliced viral transcripts. Although a unique RNA structure has been proposed for the Rev-response element (RRE) responsible for viral mRNA export, how it recruits multiple HIV Rev proteins to form an export complex has been unclear. We show here that initial binding of Rev to the RRE triggers RNA tertiary structural changes, enabling further Rev binding and the rapid formation of a viral export complex. Analysis of the Rev-RRE assembly pathway using SHAPE-Seq and small-angle X-ray scattering (SAXS) reveals two major steps of Rev-RRE complex formation, beginning with rapid Rev binding to a pre-organized region presenting multiple Rev binding sites. This step induces long-range remodeling of the RNA to expose a cryptic Rev binding site, enabling rapid assembly of additional Rev proteins into the RNA export complex. This kinetic pathway may help maintain the balance between viral replication and maturation.

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  • RRE is present in both unspliced and singly spliced RNAs, facilitating their export from the nucleus.

    “Consequently, the RRE is present in both unspliced and singly spliced RNAs, facilitating their export from the nucleus (Hadzopoulou-Cladaras et al. 1989, Malim et al. 1989, 1990, Cochrane et al. 1990, Bai et al. 2014).”

    From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Bai et al. 2014

    The Introduction (page unavailable) says unspliced HIV transcripts are exported through complexes formed when Rev binds the RRE, supporting that part of the claim. It does not say that the RRE is present in singly spliced RNAs; searches for singly and partially spliced transcripts found no non-abstract passage establishing that part. (LLM, conf=0.84)

    Experimental — accuracy not yet measured
  • Rev/RRE complex recruits CRM1 and Ran to form nuclear export complex that exports these RNAs from nucleus to cytoplasm.

    “To achieve this, the Rev/RRE complex recruits a host protein, the cellular chromosomal maintenance 1 (CRM1, also known as Exportin 1; XpoI) and Ran (RAs-related nuclear protein) also known as GTP-binding nuclear protein, to form the nuclear export complex that successfully exports these RNAs from nucleus to the cytoplasm (Fig. 9 and Table 1) (Neville et al. 1997, Askjaer et al. 1998, Bai et al. 2”

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Authors
Bai, Y., Tambe, A., Zhou, K., & Doudna, J. A.
Affiliations
  • University of California, Berkeley (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Doudna, Jennifer A
Venue
eLife
Published
2014-08-27
Volume
3
Pages
e03656-e03656
ISSN
2050-084X (ISSN-L)
OpenAlex
W2035151243
Cited by
86
References
66
Citations by year
2026: 2 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 10 · 2021: 3 · 2020: 8 · 2019: 11 · 2018: 7 · 2017: 7 · 2016: 15 · 2015: 9 · 2014: 4
FWCI
5.20
Type
journal article
Language
en
Open access
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institute of General Medical Sciences (The HARC Center, P50GM82250)
  • Howard Hughes Medical Institute
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
HIV Rev protein, Rev response element, RNA tertiary structure, HIV replication, viral mRNA splicing, small-angle X-ray scattering
MeSH terms
Binding Sites, Cell Nucleus, Eukaryotic Cells, Humans, Molecular Sequence Data, RNA Splicing, RNA, Viral, Thermodynamics, Virus Replication, X-Ray Diffraction, HIV-1, RNA, Guide, Kinetoplastida, Response Elements, Active Transport, Cell Nucleus, RNA Transport, Scattering, Small Angle, rev Gene Products, Human Immunodeficiency Virus, RNA Folding

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