Ribonucleic acids, often called a biological jack of all trades, contribute intimately to every aspect of gene expression, including the synthesis of other polypeptide biocatalysts. The fundamental importance of recurring structural motifs and the kinetics and energetics of the complex secondary and tertiary structure of RNA have been shown to be intimately linked with its functions in vivo. We have developed a novel enzymatic synthetic approach for covalent attachment of photoresponsive units into the RNA backbone. The synthetic conditions of this approach are extremely mild, involving the reverse micellar solubilization of nucleic acid along with lipase in apolar hydrocarbon solvents. Lipase catalyzed acylation of the 2' hydroxyl group in the ribose sugars of the RNA molecule has been used to incorporate photo-isomerizable azobenzene groups into the RNA strands. This micellar approach was envisaged for RNA functionalization while maintaining the conformational integrity of the macromolecular backbone in neutral buffer solution. The modification of RNA using covalently attached chromophores or fluorophores can be extended to other biomacromolecular matrices leading to the development of more versatile photoactive biopolymers. The photo-isomerizable groups incorporated in the RNA molecule can serve as optical ‘handles’ for the manipulation of the conformation of RNA and open new opportunities for biophotonic device applications.