Poster abstracts
Poster number 86 submitted by Stephanie Mack
Approaches to Synthetic Mini-lariats for RNA Interference
Stephanie Mack (Chemistry, Carnegie Mellon University), Sourav K. Dey (Chemistry, Carnegie Mellon University), Subha R. Das (Chemistry, Carnegie Mellon University)
Abstract:
RNA interference is a powerful tool to knockdown gene expression. The RNA-induced silencing complex (RISC) is the endogenous cellular machinery that destroys messenger RNA based on a target complementary that is sequence derived from microRNAs (miRNAs). A large number of miRNAs have been suggested to originate from spliced introns that must be debranched before entering RISC. We are devising mimics for these intronic miRNAs (mirtrons) by synthesizing small RNA lariats that will open up into a linearized strand upon cleavage by debranching enzyme. This strand would mimic the target complementary guide strand of the miRNA and would be taken up by RISC. Solid phase synthesis of the mini-lariats is achieved through 5'-phosphitylation and subsequent selective removal of a 2'-O-photolabile group at the desired branch nucleotide. Following the 2'-O-protecting group removal, coupling of the 5' phosphoroamidite to the free 2'-OH completes mini-lariat synthesis with a 2'-5'-phosphate linkage, a substrate for debranching enzyme. These mini-lariats are being evaluated as agents for RNA interference.
Keywords: RNA interference, micro RNA, mini-lariats