Solution Structure of the HIV-1 Intron Splicing Silencer and Its Interactions with the UP1 Domain of Heterogeneous Nuclear Ribonucleoprotein (hnRNP) A1
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. Atogether, this work provides additional insights into how HIV-1 uses a conserved RNA structure to commandeer a host RNA-binding protein.
- Authors:
-
- Case Western Reserve Univ., Cleveland, OH (United States)
- Univ. of Florida, Gainesville, FL (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Inst. of Health; National Science Foundation (NSF)
- OSTI Identifier:
- 1243109
- Grant/Contract Number:
- AC02-06CH11357; R01 GM101979; P50 GM103297; 334048; P41 GM103622; 1S10OD018090-1
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Biological Chemistry
- Additional Journal Information:
- Journal Volume: 291; Journal Issue: 5; Journal ID: ISSN 0021-9258
- Publisher:
- American Society for Biochemistry and Molecular Biology
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; alternative splicing; calorimetry; heterogeneous nuclear ribonucleoprotein (hnRNP); human immunodeficiency virus (HIV); nuclear magnetic resonance (NMR); phylogenetics
Citation Formats
Jain, Niyati, Morgan, Christopher E., Rife, Brittany D., Salemi, Marco, and Tolbert, Blanton S. Solution Structure of the HIV-1 Intron Splicing Silencer and Its Interactions with the UP1 Domain of Heterogeneous Nuclear Ribonucleoprotein (hnRNP) A1. United States: N. p., 2015.
Web. doi:10.1074/jbc.M115.674564.
Jain, Niyati, Morgan, Christopher E., Rife, Brittany D., Salemi, Marco, & Tolbert, Blanton S. Solution Structure of the HIV-1 Intron Splicing Silencer and Its Interactions with the UP1 Domain of Heterogeneous Nuclear Ribonucleoprotein (hnRNP) A1. United States. https://doi.org/10.1074/jbc.M115.674564
Jain, Niyati, Morgan, Christopher E., Rife, Brittany D., Salemi, Marco, and Tolbert, Blanton S. Tue .
"Solution Structure of the HIV-1 Intron Splicing Silencer and Its Interactions with the UP1 Domain of Heterogeneous Nuclear Ribonucleoprotein (hnRNP) A1". United States. https://doi.org/10.1074/jbc.M115.674564. https://www.osti.gov/servlets/purl/1243109.
@article{osti_1243109,
title = {Solution Structure of the HIV-1 Intron Splicing Silencer and Its Interactions with the UP1 Domain of Heterogeneous Nuclear Ribonucleoprotein (hnRNP) A1},
author = {Jain, Niyati and Morgan, Christopher E. and Rife, Brittany D. and Salemi, Marco and Tolbert, Blanton S.},
abstractNote = {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. Atogether, this work provides additional insights into how HIV-1 uses a conserved RNA structure to commandeer a host RNA-binding protein.},
doi = {10.1074/jbc.M115.674564},
journal = {Journal of Biological Chemistry},
number = 5,
volume = 291,
place = {United States},
year = {Tue Nov 24 00:00:00 EST 2015},
month = {Tue Nov 24 00:00:00 EST 2015}
}
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