2021
DOI: 10.1101/2021.10.21.465253
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The HIV-1 Integrase C-Terminal domain induces TAR RNA structural changes promoting Tat binding

Abstract: Recent evidence indicated that HIV-1 Integrase (IN) binds genomic viral RNA (gRNA) playing a critical role in viral particle morphogenesis and gRNA stability in host cells. Combining biophysical and biochemical approaches we show that the C-terminal flexible 18-residues tail of IN acts as a sensor of the peculiar apical structure of trans-activation response element RNA (TAR), directly interacting with its hexaloop. We highlighted how the whole IN C-terminal domain, once bound to TAR, can change its structure … Show more

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Cited by 4 publications
(3 citation statements)
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References 68 publications
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“…Hence, functional differences might be mediated by combined polymorphisms within integrase itself or across various retroviral proteins. One attractive candidate for such co-regulation is Tat, given recent evidence that Tat and integrase bind cooperatively with TAR in HIV-1 [63]. We anticipate that this process is conserved in HIV-2.…”
Section: Discussionmentioning
confidence: 97%
“…Hence, functional differences might be mediated by combined polymorphisms within integrase itself or across various retroviral proteins. One attractive candidate for such co-regulation is Tat, given recent evidence that Tat and integrase bind cooperatively with TAR in HIV-1 [63]. We anticipate that this process is conserved in HIV-2.…”
Section: Discussionmentioning
confidence: 97%
“…However, early expression of Gag/Pol could be important for the replication cycle in addition to their canonical roles at late replication steps. For instance, Integrase is known to interact with TAR RNA and Tat, and has been recently shown to regulate proviral DNA transcription at early time points of infection (Elliott et al, 2020; Liu et al, 2021; Rocchi et al, 2021; Winans and Goff, 2020).…”
Section: Discussionmentioning
confidence: 99%
“…Although these methods were helpful in predicting compound structures that could bind to Tat, TAR RNA, or both, further efforts were needed to confirm Tat-TAR RNA dissociation by the identified compounds. Biochemical approaches such as electrophoretic mobility shift assay (EMSA), filter binding assay, and/or scintillation proximity assay (SPA) are widely used to characterize the interaction between proteins and nucleic acids [22][23][24][25]; however, these methods require laborious work, including immobilization of TAR RNA or Tat proteins on membranes or beads, washing, and/or isotope-labeling processes. Accordingly, these methods are generally used in small-scale screenings or confirmatory tests of selected compounds.…”
Section: Introductionmentioning
confidence: 99%