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Scientific article
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Analysis of Chlamydomonas thiamin metabolism in vivo reveals riboswitch plasticity

Publication date2013
Abstract

Thiamin (vitamin B1) is an essential micronutrient needed as a cofactor for many central metabolic enzymes. Animals must have thiamin in their diet, whereas bacteria, fungi, and plants can biosynthesize it de novo from the condensation of a thiazole and a pyrimidine moiety. Although the routes to biosynthesize these two heterocycles are not conserved in different organisms, in all cases exogenous thiamin represses expression of one or more of the biosynthetic pathway genes. One important mechanism for this control is via thiamin-pyrophosphate (TPP) riboswitches, regions of the mRNA to which TPP can bind directly, thus facilitating fine-tuning to maintain homeostasis. However, there is little information on how modulation of riboswitches affects thiamin metabolism in vivo. Here we use the green alga, Chlamydomonas reinhardtii, which regulates both thiazole and pyrimidine biosynthesis with riboswitches in the THI4 (Thiamin 4) and THIC (Thiamin C) genes, respectively, to investigate this question. Our study reveals that regulation of thiamin metabolism is not the simple dogma of negative feedback control. Specifically, balancing the provision of both of the heterocycles of TPP appears to be an important requirement. Furthermore, we show that the Chlamydomonas THIC riboswitch is controlled by hydroxymethylpyrimidine pyrophosphate, as well as TPP, but with an identical alternative splicing mechanism. Similarly, the THI4 gene is responsive to thiazole. The study not only provides insight into the plasticity of the TPP riboswitches but also shows that their maintenance is likely to be a consequence of evolutionary need as a function of the organisms' environment and the particular pathway used.

Keywords
  • Algal Proteins/genetics/metabolism
  • Alternative Splicing
  • Biosynthetic Pathways/genetics
  • Chlamydomonas reinhardtii/genetics/metabolism
  • Gene Expression Regulation
  • Plant
  • Molecular Structure
  • Phosphotransferases (Phosphate Group Acceptor)/genetics/metabolism
  • Plant Proteins/genetics/metabolism
  • Point Mutation
  • Protein Binding
  • Pyrimidines/biosynthesis/chemistry
  • Reverse Transcriptase Polymerase Chain Reaction
  • Riboswitch/genetics
  • Thiamine/chemistry/metabolism
  • Thiamine Pyrophosphate/chemistry/metabolism
  • Thiazoles/chemistry/metabolism
Funding
  • Swiss National Science Foundation - Grant PP00A_119186 to TBF
  • Autre - Marie Curie Intra-European Fellowship within the Seventh European Community Framework Programme [IEF-2009-254907– RIBOREGAL (role of RIBOswitches in REGulating matabolism in ALgae); to M.M.]
Citation (ISO format)
MOULIN, Michael et al. Analysis of Chlamydomonas thiamin metabolism in vivo reveals riboswitch plasticity. In: Proceedings of the National Academy of Sciences of the United States of America, 2013, vol. 110, n° 36, p. 14622–14627. doi: 10.1073/pnas.1307741110
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Article (Published version)
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Identifiers
ISSN of the journal0027-8424
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