SYNTHETIC AND CONFORMATIONAL STUDIES OF BRANCHED AND LARIAT RNAS - MODELING THE LARIAT FORMED IN THE SPLICING REACTION - A CRITICAL-REVIEW

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 (bran ched and lariat RNGs) of the lariat RNA intron formed in the penultima te step of group II and nuclear pre-mRNA processing reaction (splicing ) in eukaryotes have been used in structural studies (NMR) to understa nd its biological importance. Some of the synthetic lariat RNAs also f unction as biomimetic models for study of the self-cleavage reaction t aking place in natural ribozyme-RNA substrate complexes. This review d eals with our work on the design and synthesis of model systems mimick ing the biological lariat RNA. All the published works on chemical syn thesis of branched and lariat oligo-RNAs have been covered in this pap er with emphasis on our own extensive work. Our synthetic schemes of a cyclic branched RNA trimers (($) under bar 1-($) under bar 7), tetrame rs (($) under bar 8-($) under bar 15), pentamers (($) under bar 16-($) under bar 17), heptamer ($) under bar 18, nonamer ($) under bar 19, d ecamer ($) under bar 20 and lariat RNA tetramer ($) under bar 21 penta mer ($) under bar 22, hexamer ($) under bar 23 and heptamer ($) under bar 24 show how delicately one had to employ different sets of complem entary protecting groups and phosphorylation-techniques for the synthe sis of the target RNAs. Despite the display of apparent complexity of these strategies, they all can be grouped under two general reaction r outes. In the final section we have given a brief summary of the resul ts of our structural studies on our synthetic branched RNAs using 500 and 600 MHz NMR spectroscopy.