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PDBsum entry 2n4l
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References listed in PDB file
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Key reference
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Title
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Solution structure of the HIV-1 intron splicing silencer and its interactions with the up1 domain of heterogeneous nuclear ribonucleoprotein (hnrnp) a1.
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Authors
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N.Jain,
C.E.Morgan,
B.D.Rife,
M.Salemi,
B.S.Tolbert.
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Ref.
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J Biol Chem, 2016,
291,
2331-2344.
[DOI no: ]
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PubMed id
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Abstract
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Splicing patterns in human immunodeficiency virus type 1 (HIV-1) are maintained
through cis regulatory elements that recruit antagonistic host RNA-binding
proteins. The activity of the 3' acceptor site A7 is tightly regulated through a
complex network of an intronic splicing silencer (ISS), a bipartite exonic
splicing silencer (ESS3a/b), and an exonic splicing enhancer (ESE3). Because
HIV-1 splicing depends on protein-RNA interactions, it is important to know the
tertiary structures surrounding the splice sites. Herein, we present the NMR
solution structure of the phylogenetically conserved ISS stem loop. ISS adopts a
stable structure consisting of conserved UG wobble pairs, a folded 2X2 (GU/UA)
internal loop, a UU bulge, and a flexible AGUGA apical loop. Calorimetric and
biochemical titrations indicate that the UP1 domain of heterogeneous nuclear
ribonucleoprotein A1 binds the ISS apical loop site-specifically and with
nanomolar affinity. Collectively, this work provides additional insights into
how HIV-1 uses a conserved RNA structure to commandeer a host RNA-binding
protein.
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Headers
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