title: Control of alternative RNA splicing and gene expression by eukaryotic riboswitches.
abstract: Bacteria make extensive use of riboswitches to sense metabolites and control gene expression, and typically do so by modulating premature transcription termination or translation initiation. The most widespread riboswitch class known in bacteria responds to the coenzyme thiamine pyrophosphate (TPP), which is a derivative of vitamin B1. Representatives of this class have also been identified in fungi and plants, where they are predicted to control messenger RNA splicing or processing. We examined three TPP riboswitches in the filamentous fungus Neurospora crassa, and found that one activates and two repress gene expression by controlling mRNA splicing. A detailed mechanism involving riboswitch-mediated base-pairing changes and alternative splicing control was elucidated for precursor NMT1 mRNAs, which code for a protein involved in TPP metabolism. These results demonstrate that eukaryotic cells employ metabolite-binding RNAs to regulate RNA splicing events that are important for the control of key biochemical processes.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Ming T
authors.initials: MT
authors.lastname: Cheah
authors.forename: Andreas
authors.initials: A
authors.lastname: Wachter
authors.forename: Narasimhan
authors.initials: N
authors.lastname: Sudarsan
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Breaker
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020029:Base Pairing; D001483:Base Sequence; D005057:Eukaryotic Cells / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D005800:Genes, Fungal / Q000235:genetics*; D007438:Introns / Q000235:genetics*; D009492:Neurospora crassa / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D012331:RNA, Fungal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D052157:Aptamers, Nucleotide; D012331:RNA, Fungal; D012333:RNA, Messenger