title: Identification of potential regulatory elements in the 5' and 3' UTRs of 12 translationally regulated mRNAs in mammalian spermatids by comparative genomics.
abstract: To facilitate identifying translational control elements by studies of  mutations in transgenic mice, a database of orthologous 5' and 3'  ends of 12 messenger RNA (mRNA) species from 13 to 23 mammals that undergo  delayed translational activation in spermatids was constructed for the  Acev2, Akap3, Akap4v2, Gapdhs,  Odf1, Prm1, Prm2, Prm3, Smcp,  Spata18, Tnp1, and Tnp2 mRNAs. This database,  available here, was searched for conserved sequences in conserved positions  and known translational control elements. Numerous potential mRNA-specific  elements were identified, including upstream open reading frames, conserved  sequences upstream and downstream of the poly(A) signal, and noncanonical and  multiple poly(A) signals. RNA electrophoresis mobility shift assays  demonstrate that Y-box proteins bind 30 of the 36 permutations of the  degenerate Y-box recognition sequence (YRS), [UAC][CA]CA[UC]C[ACU], and this  information was used to identify hundreds of YRSs in the untranslated region  (UTR) database. Collectively, these findings suggest that the distal ends of  both UTRs are particularly well conserved, implying that translation of each  mRNA is regulated by mechanisms involving the poly(A) binding protein and the  closed loop. In addition, the 5' flanking regions of all 12 genes have  conserved, gene-specific sequences and configurations of elements that  resemble the binding site of the testis-specific isoform of cyclic AMP  response element modulator, and all 12 genes lack retrogene paralogues,  demonstrating the efficacy of mechanisms that limit the proliferation of  retroposons in the male germ line. This study illustrates the power of  comparative genomics in identifying novel hypothetical regulatory elements for  analysis with biochemical and in vivo genetic approaches.
authors.affiliation: Department of Biology, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, USA.
authors.forename: Tamzid A
authors.initials: TA
authors.lastname: Chowdhury
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Kleene
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D055028:Comparative Genomic Hybridization; D017124:Conserved Sequence; D030541:Databases, Genetic; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D013087:Spermatids / Q000378:metabolism*; D024363:Transcription Initiation Site
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins