PDBsum entry 2n4l

RNA

PDB id: 2n4l

Contents

DNA/RNA

PDB id:

2n4l

Name:

RNA

Title:

Solution structure of the HIV-1 intron splicing silencer and its interactions with the up1 domain of hnrnp a1

Structure:

RNA (53-mer). Chain: a. Engineered: yes

Source:

Synthetic: yes

NMR struc:

10 models

Authors:

B.S.Tolbert,N.Jain,C.E.Morgan,B.D.Rife,M.Salemi

Key ref:

N.Jain et al. (2016). 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. PubMed id: 26607354 DOI: 10.1074/jbc.M115.674564

Date:

23-Jun-15 Release date: 02-Dec-15

DNA/RNA chain

G-G-A-A-U-A-U-U-U-U-U-G-C-U-G-U-A-C-U-U-U-C-U-A-U-A-G-U-G-A-A-U-A-G-A-G-U-U-A- 53 bases

DOI no: 10.1074/jbc.M115.674564

J Biol Chem 291:2331-2344 (2016)

PubMed id: 26607354

Solution Structure of the HIV-1 Intron Splicing Silencer and Its Interactions with the UP1 Domain of Heterogeneous Nuclear Ribonucleoprotein (hnRNP) A1.

N.Jain, C.E.Morgan, B.D.Rife, M.Salemi, B.S.Tolbert.

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.