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Article Dans Une Revue Biochemical Journal Année : 2010

The HDHD1 gene, often deleted in X-linked ichthyosis, encodes a pseudouridine-5'-phosphatase

Alice Preumont
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Rim Rzem
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Didier Vertommen
Emile van Schaftingen
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Résumé

Pseudouridine, the fifth most abundant nucleoside in RNA, is not metabolised in mammals, but is excreted intact in urine. The purpose of the present work was to search for an enzyme that would dephosphorylate pseudouridine 5'-phosphate, a potential intermediate in RNA degradation. We show that human erythrocytes contain a pseudouridine-5'-phosphatase displaying a Km ≤ 1 µM for its substrate. The activity of the partially purified enzyme was dependent on Mg2+, and was inhibited by Ca2+ and by vanadate, suggesting that it belonged the ‘haloacid dehalogenase' family of phosphatases. Its low molecular mass (26 kDa) suggested that this phosphatase could correspond to the protein encoded by the HDHD1 (previously called GS1) gene, present next to the STS (steroid sulfatase) gene on human chromosome Xp22. Purified human recombinant HDHD1 dephosphorylated pseudouridine 5'-phosphate with a kcat of 1.6 s-1, a Km of 0.3 µM, and a catalytic efficiency at least 1000 fold higher than that on which it acted on other phosphate esters, including 5'-UMP. The molecular identity of pseudouridine-5'-phosphatase was confirmed by the finding that its activity was negligible (< 10% of controls) in extracts of B-cell lymphoblasts or erythrocytes from X-linked ichthyosis patients harbouring a combined deletion of the STS gene (the X-linked ichthyosis gene) and the HDHD1 gene. Furthermore, pseudouridine-5'-phosphatase activity was 1.5-fold higher in erythrocytes from women compared to men, in agreement with the HDHD1 gene undergoing only partial inactivation in females. In conclusion, HDHD1 is a phosphatase specifically involved in dephosphorylation of a modified nucleotide present in RNA.

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Dates et versions

hal-00521555 , version 1 (28-09-2010)

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Alice Preumont, Rim Rzem, Didier Vertommen, Emile van Schaftingen. The HDHD1 gene, often deleted in X-linked ichthyosis, encodes a pseudouridine-5'-phosphatase. Biochemical Journal, 2010, 431 (2), pp.237-244. ⟨10.1042/BJ20100174⟩. ⟨hal-00521555⟩

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