The use of contemporary nuclear magnetic resonance (NMR) methods in the studies of model systems between microRNA (miRNA) and messenger RNA (mRNA) is reviewed. We describe our studies on structural features of 33-nt RNA model construct between let-7 miRNA and lin-41 mRNA at the second binding site. let-7 miRNA inhibits translation of lin-41 gene through formation of two complexes with the target sequence within 3' untranslated region of lin-41 mRNA in Caenorhabditis elegans. The base pairing, asymmetric internal loops, and adenine bulge in both the complementary sites are important for regulation of gene expression. NMR study on the uniformly (13)C- and (15)N-labeled RNA construct has shown that RNA molecule folds into a stable structure consisting of two stem regions separated by a well-defined asymmetric internal loop. Solution-state NMR can make important contribution toward deeper understanding of assembly, folding, and structural features of miRNA:mRNA complexes.