1. Department of Molecular, Cellular and Developmental Biology;
2. Department of Molecular Biophysics and Biochemistry;
3. Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06520, USA
4. These authors contributed equally to this work.

Correspondence to: Ronald R. Breaker^1,2,3 Correspondence and requests for materials should be addressed to R.R.B. (Email: ronald.breaker@yale.edu).

Abstract

Bacteria make extensive use of riboswitches^{1, 2} 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)^{3, 4}, which is a derivative of vitamin B₁. Representatives of this class have also been identified^{5, 6} in fungi and plants, where they are predicted^{5, 7} 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.

1. Department of Molecular, Cellular and Developmental Biology;
2. Department of Molecular Biophysics and Biochemistry;
3. Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06520, USA
4. These authors contributed equally to this work.

Correspondence to: Ronald R. Breaker^1,2,3 Correspondence and requests for materials should be addressed to R.R.B. (Email: ronald.breaker@yale.edu).

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