Synthetic and conformational studies of branched and lariat RNAs. Modelling the lariat formed in the splicing reaction — A critical review

Abstract

The formation of lariat RNAs in eukaryotes plays a central role in the transmission of genetic information into protein products through the synthesis of the processed RNA. The biomimetic synthetic models (branched and lariat RNAs) of the lariat RNA intron formed in the penultimate step of group II and nuclear pre-mRNA processing reaction (splicing) in eukaryotes have been used in structural studies (NMR) to understand its biological importance. Some of the synthetic lariat RNAs also function as biomimetic models for study of the self-cleavage reaction taking place in natural ribozyme-RNA substrate complexes. This review deals with our work on the design and synthesis of model systems mimicking the biological lariat RNA. All the published works on chemical synthesis of branched and lariat oligo-RNAs have been covered in this paper with emphasis on our own extensive work. Our synthetic schemes of acyclic branched RNA trimers (1–7), tetramers (8–5), pentamers (16, 17), heptamer 18, nonamer 19, decamer 20 and lariat RNA tetramer 21, pentamer 22, hexamer 23 and heptamer 24 show how delicately one had to employ different sets of complementary protecting groups and phosphorylation techniques for the synthesis of the target RNAs. Despite the display of apparent complexity of these strategies, they all can be grouped under two general reaction routes. In the final section we have given a brief summary of the results of our structural studies on our synthetic branched RNAs using 500 and 600 MHz NMR spectroscopy.