title: RNA structure in splicing: An evolutionary perspective.
abstract: Pre-mRNA splicing is a key post-transcriptional regulation process in which introns are excised and exons are ligated together. A novel class of structured intron was recently discovered in fish. Simple expansions of complementary AC and GT dimers at opposite boundaries of an intron were found to form a bridging structure, thereby enforcing correct splice site pairing across the intron. In some fish introns, the RNA structures are strong enough to bypass the need of regulatory protein factors for splicing. Here, we discuss the prevalence and potential functions of highly structured introns. In humans, structured introns usually arise through the co-occurrence of C and G-rich repeats at intron boundaries. We explore the potentially instructive example of the HLA receptor genes. In HLA pre-mRNA, structured introns flank the exons that encode the highly polymorphic β sheet cleft, making the processing of the transcript robust to variants that disrupt splicing factor binding. While selective forces that have shaped HLA receptor are fairly atypical, numerous other highly polymorphic genes that encode receptors contain structured introns. Finally, we discuss how the elevated mutation rate associated with the simple repeats that often compose structured intron can make structured introns themselves rapidly evolving elements.
authors.affiliation: a Molecular Biology, Cell Biology and Biochemistry, Brown University , Providence , RI , USA.
authors.forename: Chien-Ling
authors.initials: CL
authors.lastname: Lin
authors.affiliation: a Molecular Biology, Cell Biology and Biochemistry, Brown University , Providence , RI , USA.
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Taggart
authors.affiliation: a Molecular Biology, Cell Biology and Biochemistry, Brown University , Providence , RI , USA.|b Center for Computational Molecular Biology, Brown University , Providence , RI , USA.|c Hassenfeld Child Health Innovation Institute of Brown University , Providence , RI , USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Fairbrother
mesh_terms: D000818:Animals; D005075:Biological Evolution; D005091:Exons; D006801:Humans; D007438:Introns; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide; D012313:RNA / Q000737:chemistry* / Q000235:genetics*; D012322:RNA Precursors / Q000737:chemistry / Q000235:genetics; D012326:RNA Splicing; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D000072668:Splicing Factor U2AF / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D012322:RNA Precursors; D012333:RNA, Messenger; D000072668:Splicing Factor U2AF; D012313:RNA
keywords: Dinucleotide repeats; U2AF2; intron secondary structure; pre-mRNA splicing; single nucleotide polymorphism