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Cover Picture: Site-Specific Modification of Epstein–Barr Virus-Encoded RNA 1 with N2-Benzylguanosine Limits the Binding Sites Occupied by PKR (ChemBioChem 3/2004)
The cover picture shows the use of site-specific incorporation of N2-benzylguanosine into RNA as a method for controlling the binding sites occupied by proteins that contain double-stranded RNA binding motifs (dsRBMs). A fragment of the Epstein–Barr virus-encoded RNA 1 (EBER1) binds dsRBM I from the RNA-dependent protein kinase (PKR) at two sites. Based on data from affinity cleavage experiments and molecular modeling, nucleotide positions were chosen in this RNA for incorporation of N2-benzyl guanosine, which places a bulky benzyl group in the minor groove of the RNA duplex. These site-specific modifications lead to controlled inhibition of binding by PKR at the two different sites. This simple but effective technique can be further used to study similar dsRBM–RNA complexes. Modifications of duplex RNA like this that prevent dsRBMs from binding may be necessary in the development of RNA interference reagents (siRNAs) that will not interact with PKR or other double-stranded RNA binding proteins. For more details see the article by P. A. Beal et al. on p. 383 ff.