2N4L: Solution Structure Of The Hiv-1 Intron Splicing Silencer And Its Interactions With The Up1 Domain Of Hnrnp A1

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.
PDB ID: 2N4LDownload
MMDB ID: 134505
PDB Deposition Date: 2015/6/23
Updated in MMDB: 2015/12
Experimental Method:
solution nmr
Biological Unit for 2N4L: monomeric; determined by author
Molecular Components in 2N4L
Label Count Molecule
Nucleotide(1 molecule)
RNA (53-mer)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB