title: Regiospecific solid-phase synthesis of branched oligoribonucleotides that mimic intronic lariat RNA intermediates.
abstract: We have developed new solid phase methods for the synthesis of branched RNAs that mimic intronic lariat RNA intermediates. These methods produce branched oligoribonucleotide sequences of arbitrary length, base composition, and regiochemistry at the branchpoint junction. The methods utilize branching monomers that allow for the growth of each branch regioselectively from any of the hydroxyl positions (5′, 3′, or 2′) at the branch-point junction. The integrity and branchpoint connectivity of the synthetic products have been confirmed by HPLC and MS analysis, and cleavage of the 2′,5′ linkage by recombinant debranching enzyme. Nonhydrolyzable branched RNA analogues containing arabinose instead of ribose at the branchpoint junction were shown to inhibit debranching activity and, hence, represent “decoys” for sequestering RNA binding proteins thought to drive amyotrophic lateral sclerosis (ALS).
authors.forename: Adam
authors.initials: A
authors.lastname: Katolik
authors.forename: Richard
authors.initials: R
authors.lastname: Johnsson
authors.forename: Eric
authors.initials: E
authors.lastname: Montemayor
authors.forename: Jeremy G
authors.initials: JG
authors.lastname: Lackey
authors.forename: P John
authors.initials: PJ
authors.lastname: Hart
authors.forename: Masad J
authors.initials: MJ
authors.lastname: Damha
mesh_terms: D001483:Base Sequence; D009690:Nucleic Acid Conformation; D009843:Oligoribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques
chemical_list: D009843:Oligoribonucleotides; D016601:RNA-Binding Proteins; D012313:RNA