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

Journal Article · · Journal of Biological Chemistry
 [1];  [1];  [2];  [2];  [1]
  1. Case Western Reserve Univ., Cleveland, OH (United States)
  2. Univ. of Florida, Gainesville, FL (United States)
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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. Atogether, this work provides additional insights into how HIV-1 uses a conserved RNA structure to commandeer a host RNA-binding protein.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Inst. of Health; National Science Foundation (NSF)
Grant/Contract Number:
AC02-06CH11357; R01 GM101979; P50 GM103297; 334048; P41 GM103622; 1S10OD018090-1
OSTI ID:
1243109
Journal Information:
Journal of Biological Chemistry, Vol. 291, Issue 5; ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular BiologyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 21 works
Citation information provided by
Web of Science

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Cited By (3)

Rules of RNA specificity of hnRNP A1 revealed by global and quantitative analysis of its affinity distribution journal February 2017
Analysis of a structured intronic region of the LMP2 pre-mRNA from EBV reveals associations with human regulatory proteins and nuclear actin journal January 2019
Characterizing HIV-1 Splicing by Using Next-Generation Sequencing text January 2017

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
alternative splicing
calorimetry
heterogeneous nuclear ribonucleoprotein (hnRNP)
human immunodeficiency virus (HIV)
nuclear magnetic resonance (NMR)
phylogenetics