2N4L

Solution Structure of the HIV-1 Intron Splicing Silencer and its Interactions with the UP1 Domain of hnRNP A1

Summary for 2N4L

• Entry DOI: 10.2210/pdb2n4l/pdb
• NMR Information: BMRB: 25671
• Descriptor: RNA (53-MER) (1 entity in total)
• Functional Keywords: hiv intronic splicing silencer, rna alternative splicing, rna
• Total number of polymer chains: 1
• Total formula weight: 17006.00

Authors

Tolbert, B.S.,Jain, N.,Morgan, C.E.,Rife, B.D.,Salemi, M. (deposition date: 2015-06-23, release date: 2015-12-02, Last modification date: 2024-05-01)

Primary citation

Jain, N.,Morgan, C.E.,Rife, B.D.,Salemi, M.,Tolbert, B.S.
Solution Structure of the HIV-1 Intron Splicing Silencer and Its Interactions with the UP1 Domain of Heterogeneous Nuclear Ribonucleoprotein (hnRNP) A1.
J.Biol.Chem., 291:2331-2344, 2016

PubMed Abstract: 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.

PubMed: 26607354
DOI: 10.1074/jbc.M115.674564

Experimental method

SOLUTION NMR