title: Length suppression in histone messenger RNA 3'-end maturation: processing defects of insertion mutant premessenger RNAs can be compensated by insertions into the U7 small nuclear RNA.
abstract: Efficient 3'-end processing of cell cycle-regulated mammalian histone premessenger RNAs (pre-mRNAs) requires an upstream stem-loop and a histone downstream element (HDE) that base pairs with the U7 small ribonucleoprotein. Insertions between these elements have two effects: the site of cleavage moves in concert with the HDE and processing efficiency declines. We used Xenopus oocytes to ask whether compensatory length insertions in the human U7 RNA could restore the fidelity and efficiency of processing of mouse histone insertion pre-mRNAs. An insertion of 5 nt into U7 RNA that extends its complementary to the HDE compensated for both defects in processing of a 5-nt insertion substrate; a noncomplementary insertion into U7 did not. Yet, the noncomplementary insertion mutant U7 was shown to be active on insertion substrates further mutated to allow base pairing. Our results suggest that the histone pre-mRNA becomes rigidified upstream of its HDE, allowing the bound U7 small ribonucleoprotein to measure from the HDE to the cleavage site. Such a mechanism may be common to other RNA measuring systems. To our knowledge, this is the first demonstration of length suppression in an RNA processing system.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536-0812, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Scharl
authors.forename: J A
authors.initials: JA
authors.lastname: Steitz
mesh_terms: D000818:Animals; D001483:Base Sequence; D006657:Histones / Q000235:genetics*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D012322:RNA Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D012342:RNA, Small Nuclear / Q000235:genetics*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics*; D014981:Xenopus
chemical_list: D006657:Histones; D012322:RNA Precursors; D012333:RNA, Messenger; D012342:RNA, Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear