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Title

Analysis of Chlamydomonas thiamin metabolism in vivo reveals riboswitch plasticity

Authors
Nguyen, Ginnie T D T
Scaife, Mark A
Smith, Alison G
Published in Proceedings of the National Academy of Sciences. 2013, vol. 110, no. 36, p. 14622-14627
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/metabolismAlternative SplicingBiosynthetic Pathways/geneticsChlamydomonas reinhardtii/genetics/metabolismGene Expression RegulationPlantMolecular StructurePhosphotransferases (Phosphate Group Acceptor)/genetics/metabolismPlant Proteins/genetics/metabolismPoint MutationProtein BindingPyrimidines/biosynthesis/chemistryReverse Transcriptase Polymerase Chain ReactionRiboswitch/geneticsThiamine/chemistry/metabolismThiamine Pyrophosphate/chemistry/metabolismThiazoles/chemistry/metabolism
Identifiers
PMID: 23959877
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Structures
Projects FNS: Grant PP00A_119186 to TBF
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.]
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MOULIN, Michael et al. Analysis of Chlamydomonas thiamin metabolism in vivo reveals riboswitch plasticity. In: Proceedings of the National Academy of Sciences, 2013, vol. 110, n° 36, p. 14622-14627. https://archive-ouverte.unige.ch/unige:89270

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Deposited on : 2016-11-22

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