9W1L

NMR Structure of the 5BSL3.2 Apical Stem-Loop RNA from HCV

Summary for 9W1L

• Entry DOI: 10.2210/pdb9w1l/pdb
• NMR Information: BMRB: 53244
• Descriptor: RNA (26-MER) (1 entity in total)
• Functional Keywords: hcv cre domain stem loop 2, rna
• Biological source: Hepatitis C virus (isolate 1)
• Total number of polymer chains: 1
• Total formula weight: 8263.96

Authors

Kumar, A.,Penumutchu, S.,Deshmukh, M.V.,Jain, N. (deposition date: 2025-07-26, release date: 2026-01-28)

Primary citation

Kumar, A.,Penumutchu, S.,Panchariya, L.,Kumari, P.,Thakur, S.,Daripa, P.,Singh, V.,Arulandu, A.,Maiti, S.,Deshmukh, M.V.,Jain, N.
Loop of fate: structural and mechanistic insights into hnRNPA1 binding to the hepatitis C virus RNA.
Rna, 32:215-236, 2026

PubMed Abstract: Hepatitis C virus (HCV) is a major global health burden, associated with chronic liver diseases, including cirrhosis and hepatocellular carcinoma. Viral replication critically depends on conserved -acting replication elements (CREs), such as the 5BSL3.2 stem-loop near the 3' end of the open reading frame. This element forms a long-range kissing-loop interaction with the SL2 domain of the 3'X tail, essential for efficient genome replication. However, the role of host RNA-binding proteins (RBPs) in regulating this RNA-RNA interaction remains poorly understood. To explore this, we investigated whether the host RBP hnRNPA1 modulates HCV replication by targeting the 5BSL3.2 element. Using an integrated approach combining structural biology, biophysics, and biochemical assays, we identify the terminal loop of 5BSL3.2 as a high-affinity binding site for the tandem RNA recognition motifs (RRMs) of hnRNPA1. Our data reveal that adenine-rich residues within the loop are critical for binding specificity. Our results uncover a structural mechanism by which hnRNPA1 binding perturbs the kissing-loop interaction between 5BSL3.2 and the SL2 element of the viral 3'X-tail, which impacts viral replication. This study highlights a previously unrecognized role of hnRNPA1 in modulating viral RNA structure and suggests a novel interface for host-directed antiviral intervention.

PubMed: 41285614
DOI: 10.1261/rna.080770.125

Experimental method

SOLUTION NMR