title: RNA structure replaces the need for U2AF2 in splicing.
abstract: RNA secondary structure plays an integral role in catalytic, ribosomal, small nuclear, micro, and transfer RNAs. Discovering a prevalent role for secondary structure in pre-mRNAs has proven more elusive. By utilizing a variety of computational and biochemical approaches, we present evidence for a class of nuclear introns that relies upon secondary structure for correct splicing. These introns are defined by simple repeat expansions of complementary AC and GT dimers that co-occur at opposite boundaries of an intron to form a bridging structure that enforces correct splice site pairing. Remarkably, this class of introns does not require U2AF2, a core component of the spliceosome, for its processing. Phylogenetic analysis suggests that this mechanism was present in the ancestral vertebrate lineage prior to the divergence of tetrapods from teleosts. While largely lost from land dwelling vertebrates, this class of introns is found in 10% of all zebrafish genes.
authors.affiliation: Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA;
authors.forename: Chien-Ling
authors.initials: CL
authors.lastname: Lin
authors.affiliation: Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA;
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Taggart
authors.affiliation: Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA;
authors.forename: Kian Huat
authors.initials: KH
authors.lastname: Lim
authors.affiliation: Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA; Center for Computational Molecular Biology, Brown University, Providence, Rhode Island 02912, USA;
authors.forename: Kamil J
authors.initials: KJ
authors.lastname: Cygan
authors.affiliation: Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA;
authors.forename: Luciana
authors.initials: L
authors.lastname: Ferraris
authors.affiliation: Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA;
authors.forename: Robbert
authors.initials: R
authors.lastname: Creton
authors.affiliation: Departments of Epidemiology and Biostatistics, Brown University, Providence, Rhode Island 02912, USA.
authors.forename: Yen-Tsung
authors.initials: YT
authors.lastname: Huang
authors.affiliation: Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA; Center for Computational Molecular Biology, Brown University, Providence, Rhode Island 02912, USA;
authors.forename: William G
authors.initials: WG
authors.lastname: Fairbrother
mesh_terms: D000818:Animals; D001483:Base Sequence; D019295:Computational Biology; D005091:Exons; D017930:Genes, Reporter; D007438:Introns; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D017381:Spliceosomes / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; D012322:RNA Precursors; D012261:Ribonucleoproteins