NMR Analysis Suggests Synergy between the RRM2 and the Carboxy-Terminal Segment of Human La Protein in the Recognition and Interaction with HCV IRES

The La protein (lupus antigen) is a ubiquitous RNA-binding protein found in all human cells. It is mainly localized in the nucleus, associates with all RNA polymerase III (Pol III) transcripts, as the first factor they interact with, and modulates subsequent processing events. Export of La to the cytoplasm has been reported to stimulate the decoding of specific cellular and viral mRNAs through IRES-dependent (Internal ribosome entry site) binding and translation. Using NMR (Nuclear Magnetic Resonance) spectroscopy, we provide atomic-level-resolution structural insights on the dynamical properties of human La (hLa) protein in solution. Moreover, using a combination of NMR spectroscopy and isothermal titration calorimetry (ITC), we provide evidence about the role and ligand specificity of the C-terminal domain of the La protein (RRM2 and C-terminal region) that could mediate the recognition of HCV-IRES.

Automated summary

The La protein is an RNA-binding protein found in all human cells, mainly localized in the nucleus. It interacts with RNA polymerase III transcripts and modulates subsequent processing events. Export of La to the cytoplasm stimulates the decoding of specific cellular and viral mRNAs through IRES-dependent binding and translation. Atomic-level-resolution structural insights on human La protein in solution and evidence about the role of the C-terminal domain in recognizing HCV-IRES are provided using NMR spectroscopy and ITC.