title: Structurally diverse low molecular weight activators of the mammalian pre-mRNA 3' cleavage reaction.
abstract: The 3' end formation of mammalian pre-mRNA contributes to gene expression regulation by setting the downstream boundary of the 3' untranslated region, which in many genes carries regulatory sequences. A large number of protein cleavage factors participate in this pre-mRNA processing step, but chemical tools to manipulate this process are lacking. Guided by a hypothesis that a PPM1 family phosphatase negatively regulates the 3' cleavage reaction, we have found a variety of new small molecule activators of the in vitro reconstituted pre-mRNA 3' cleavage reaction. New activators include a cyclic peptide PPM1D inhibitor, a dipeptide with modifications common to histone tails, abscisic acid and an improved l-arginine β-naphthylamide analog. The minimal concentration required for in vitro cleavage has been improved from 200μM to the 200nM-100μM range. These compounds provide unexpected leads in the search for small molecule tools able to affect pre-mRNA 3' end formation.
authors.affiliation: Department of Chemistry, The City College of New York, The City University of New York, New York, NY 10031, USA.
authors.forename: Min Ting
authors.initials: MT
authors.lastname: Liu
authors.affiliation: Department of Chemistry, The City College of New York, The City University of New York, New York, NY 10031, USA.
authors.forename: Nagaraja N
authors.initials: NN
authors.lastname: Nagre
authors.affiliation: Department of Chemistry, The City College of New York, The City University of New York, New York, NY 10031, USA. Electronic address: kr107@sci.ccny.cuny.edu.
authors.forename: Kevin
authors.initials: K
authors.lastname: Ryan
mesh_terms: D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D008970:Molecular Weight; D010456:Peptides, Cyclic / Q000494:pharmacology*; D026721:RNA 3' End Processing / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D010456:Peptides, Cyclic
keywords: 3′ end formation; Histone code; Naphthalene ring; Polyadenylation; RNA; RNA processing; Small molecule activators