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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.
J Biol Chem. 2016 Jan 29; 291(5):2331-44.JB

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.

Authors+Show Affiliations

From the Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106-7078 and.From the Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106-7078 and.Department of Pathology, Immunology, and Laboratory of Medicine, College of Medicine and Emerging Pathogens Institute, University of Florida, Gainesville, Florida 32610-3633.Department of Pathology, Immunology, and Laboratory of Medicine, College of Medicine and Emerging Pathogens Institute, University of Florida, Gainesville, Florida 32610-3633.From the Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106-7078 and bst18@case.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

26607354

Citation

Jain, Niyati, et al. "Solution Structure of the HIV-1 Intron Splicing Silencer and Its Interactions With the UP1 Domain of Heterogeneous Nuclear Ribonucleoprotein (hnRNP) A1." The Journal of Biological Chemistry, vol. 291, no. 5, 2016, pp. 2331-44.
Jain N, Morgan CE, Rife BD, et al. 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. 2016;291(5):2331-44.
Jain, N., Morgan, C. E., Rife, B. D., Salemi, M., & Tolbert, B. S. (2016). Solution Structure of the HIV-1 Intron Splicing Silencer and Its Interactions with the UP1 Domain of Heterogeneous Nuclear Ribonucleoprotein (hnRNP) A1. The Journal of Biological Chemistry, 291(5), 2331-44. https://doi.org/10.1074/jbc.M115.674564
Jain N, et al. 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. 2016 Jan 29;291(5):2331-44. PubMed PMID: 26607354.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Solution Structure of the HIV-1 Intron Splicing Silencer and Its Interactions with the UP1 Domain of Heterogeneous Nuclear Ribonucleoprotein (hnRNP) A1. AU - Jain,Niyati, AU - Morgan,Christopher E, AU - Rife,Brittany D, AU - Salemi,Marco, AU - Tolbert,Blanton S, Y1 - 2015/11/24/ PY - 2015/06/29/received PY - 2015/11/27/entrez PY - 2015/11/27/pubmed PY - 2016/6/16/medline KW - alternative splicing KW - calorimetry KW - heterogeneous nuclear ribonucleoprotein (hnRNP) KW - human immunodeficiency virus (HIV) KW - nuclear magnetic resonance (NMR) KW - phylogenetics SP - 2331 EP - 44 JF - The Journal of biological chemistry JO - J Biol Chem VL - 291 IS - 5 N2 - 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. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/26607354/Solution_Structure_of_the_HIV_1_Intron_Splicing_Silencer_and_Its_Interactions_with_the_UP1_Domain_of_Heterogeneous_Nuclear_Ribonucleoprotein__hnRNP__A1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)36071-3 DB - PRIME DP - Unbound Medicine ER -