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The three-way junction structure of the HIV-1 PBS-segment binds host enzyme important for viral infectivity.

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Song Z, Gremminger T, Singh G, Cheng Y, Li J, Qiu L, Ji J, Lange MJ, Zuo X, Chen SJ, Zou X, Boris-Lawrie K, Heng X
OpenAccess logo Nucleic Acids Res 49 5925-5942 (2021)
Cited: 8 times
EuropePMC logo PMID: 33978756

Abstract

HIV-1 reverse transcription initiates at the primer binding site (PBS) in the viral genomic RNA (gRNA). Although the structure of the PBS-segment undergoes substantial rearrangement upon tRNALys3 annealing, the proper folding of the PBS-segment during gRNA packaging is important as it ensures loading of beneficial host factors. DHX9/RNA helicase A (RHA) is recruited to gRNA to enhance the processivity of reverse transcriptase. Because the molecular details of the interactions have yet to be defined, we solved the solution structure of the PBS-segment preferentially bound by RHA. Evidence is provided that PBS-segment adopts a previously undefined adenosine-rich three-way junction structure encompassing the primer activation stem (PAS), tRNA-like element (TLE) and tRNA annealing arm. Disruption of the PBS-segment three-way junction structure diminished reverse transcription products and led to reduced viral infectivity. Because of the existence of the tRNA annealing arm, the TLE and PAS form a bent helical structure that undergoes shape-dependent recognition by RHA double-stranded RNA binding domain 1 (dsRBD1). Mutagenesis and phylogenetic analyses provide evidence for conservation of the PBS-segment three-way junction structure that is preferentially bound by RHA in support of efficient reverse transcription, the hallmark step of HIV-1 replication.

Reviews - 7lva mentioned but not cited (1)

  1. Structural and computational studies of HIV-1 RNA. Levintov L, Vashisth H. RNA Biol 21 1-32 (2024)

Articles - 7lva mentioned but not cited (1)

  1. The three-way junction structure of the HIV-1 PBS-segment binds host enzyme important for viral infectivity. Song Z, Gremminger T, Singh G, Cheng Y, Li J, Qiu L, Ji J, Lange MJ, Zuo X, Chen SJ, Zou X, Boris-Lawrie K, Heng X. Nucleic Acids Res 49 5925-5942 (2021)


Reviews citing this publication (2)

  1. Anomalous HIV-1 RNA, How Cap-Methylation Segregates Viral Transcripts by Form and Function. Boris-Lawrie K, Singh G, Osmer PS, Zucko D, Staller S, Heng X. Viruses 14 935 (2022)
  2. Interplay between Host tRNAs and HIV-1: A Structural Perspective. Zhang J. Viruses 13 1819 (2021)

Articles citing this publication (4)

  1. HIV-1 hypermethylated guanosine cap licenses specialized translation unaffected by mTOR. Singh G, Seufzer B, Song Z, Zucko D, Heng X, Boris-Lawrie K. Proc Natl Acad Sci U S A 119 e2105153118 (2022)
  2. Alu RNA fold links splicing with signal recognition particle proteins. Borovská I, Vořechovský I, Královičová J. Nucleic Acids Res 51 8199-8216 (2023)
  3. Identification of a putative Gag binding site critical for feline immunodeficiency virus genomic RNA packaging. Krishnan A, Ali LM, Prabhu SG, Pillai VN, Chameettachal A, Vivet-Boudou V, Bernacchi S, Mustafa F, Marquet R, Rizvi TA. RNA 30 68-88 (2023)
  4. Structural diversity of the region encompassing DIS, SD and Psi hairpins in HIV and SIV genomes. Zarudnaya MI, Potyahaylo AL, Kolomiets IM, Gorb LG. Virus Res 336 199197 (2023)


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