title: Eukaryotic TPP riboswitch regulation of alternative splicing involving long-distance base pairing.
abstract: Thiamin pyrophosphate (TPP) riboswitches are found in organisms from all three domains of life. Examples in bacteria commonly repress gene expression by terminating transcription or by blocking ribosome binding, whereas most eukaryotic TPP riboswitches are predicted to regulate gene expression by modulating RNA splicing. Given the widespread distribution of eukaryotic TPP riboswitches and the diversity of their locations in precursor messenger RNAs (pre-mRNAs), we sought to examine the mechanism of alternative splicing regulation by a fungal TPP riboswitch from Neurospora crassa, which is mostly located in a large intron separating protein-coding exons. Our data reveal that this riboswitch uses a long-distance (∼530-nt separation) base-pairing interaction to regulate alternative splicing. Specifically, a portion of the TPP-binding aptamer can form a base-paired structure with a conserved sequence element (α) located near a 5' splice site, which greatly increases use of this 5' splice site and promotes gene expression. Comparative sequence analyses indicate that many fungal species carry a TPP riboswitch with similar intron architecture, and therefore the homologous genes in these fungi are likely to use the same mechanism. Our findings expand the scope of genetic control mechanisms relying on long-range RNA interactions to include riboswitches.
authors: Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA.
authors: Sanshu
authors: S
authors: Li
authors: Ronald R
authors: RR
authors: Breaker
mesh_terms: D017398:Alternative Splicing; D052157:Aptamers, Nucleotide; D020029:Base Pairing; D001483:Base Sequence; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D017930:Genes, Reporter; D055029:Inverted Repeat Sequences; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009492:Neurospora crassa / Q000235:genetics*; D009690:Nucleic Acid Conformation; D022821:RNA Splice Sites; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058928:Riboswitch; D013835:Thiamine Pyrophosphate / Q000235:genetics* / Q000502:physiology
chemical_list: D052157:Aptamers, Nucleotide; D022821:RNA Splice Sites; D012331:RNA, Fungal; D012333:RNA, Messenger; D058928:Riboswitch; D008156:Luciferases; D013835:Thiamine Pyrophosphate
references: FEBS Lett. 2003 Dec 18;555(3):516-20
references: 14675766
references: Nucleic Acids Res. 2009 Aug;37(14):4533-44
references: 19465384
references: Science. 2008 Mar 28;319(5871):1795-7
references: 18369140
references: Cell. 1985 Dec;43(3 Pt 2):667-76
references: 4075405
references: Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12467-72
references: 9356473
references: Cold Spring Harb Perspect Biol. 2011 Jun 01;3(6):
references: 20943759
references: PLoS Genet. 2011 Jun;7(6):e1002151
references: 21731506
references: RNA Biol. 2010 Jan-Feb;7(1):67-76
references: 20009507
references: Plant Cell. 2007 Nov;19(11):3437-50
references: 17993623
references: Genes Dev. 2007 Nov 15;21(22):2874-9
references: 18006684
references: EMBO J. 1987 Dec 1;6(12):3833-9
references: 3322814
references: RNA. 2007 Apr;13(4):573-82
references: 17307816
references: Genome Biol. 2007;8(11):R239
references: 17997835
references: Proc Natl Acad Sci U S A. 2003 May 13;100(10):5914-9
references: 12714686
references: RNA Biol. 2010 May-Jun;7(3):328-32
references: 20458165
references: Curr Opin Struct Biol. 2009 Jun;19(3):251-9
references: 19303767
references: RNA. 2003 Jun;9(6):644-7
references: 12756322
references: Mol Cell Biol. 1987 Sep;7(9):3194-8
references: 3670310
references: RNA. 2012 Jan;18(1):1-15
references: 22128342
references: Curr Opin Microbiol. 2009 Apr;12(2):161-9
references: 19250859
references: Cell. 2002 Nov 27;111(5):747-56
references: 12464185
references: Future Microbiol. 2009 Sep;4(7):771-3
references: 19722830
references: Nature. 2007 May 24;447(7143):497-500
references: 17468745
references: Mol Cell. 2011 Sep 16;43(6):867-79
references: 21925376
references: Structure. 2006 Sep;14(9):1459-68
references: 16962976
references: RNA. 1995 Jun;1(4):425-36
references: 7493320
references: Nucleic Acids Res. 2003 Apr 1;31(7):1974-83
references: 12655015
references: Science. 2006 May 26;312(5777):1208-11
references: 16675665
references: Annu Rev Biochem. 2009;78:305-34
references: 19298181
references: Mol Microbiol. 2011 Jun;80(5):1148-54
references: 21477128
references: RNA Biol. 2010 Jan-Feb;7(1):104-10
references: 20061810
references: Nature. 2002 Oct 31;419(6910):952-6
references: 12410317
references: Cell. 2005 Oct 7;123(1):65-73
references: 16213213
references: Nature. 2006 Jun 29;441(7097):1167-71
references: 16728979
references: Eukaryot Cell. 2008 Jan;7(1):28-37
references: 17766461
references: Cold Spring Harb Perspect Biol. 2012 Feb 01;4(2):
references: 21106649
references: Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20770-5
references: 18093957
references: J Biol Chem. 2002 Dec 13;277(50):48949-59
references: 12376536
references: Nature. 2003 Apr 24;422(6934):859-68
references: 12712197
references: Curr Opin Genet Dev. 2011 Aug;21(4):373-9
references: 21530232