Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome

Christelle Arrondel; Sophia Missoury; Rozemarijn Snoek; Julie Patat; Giulia Menara; Bruno Collinet; Dominique Liger; Dominique Durand; Olivier Gribouval; Olivia Boyer; Laurine Buscara; Gaëlle Martin; Eduardo Machuca; Fabien Nevo; Ewen Lescop; Daniela A. Braun; Anne Claire Boschat; Sylvia Sanquer; Ida Chiara Guerrera; Patrick Revy; Mélanie Parisot; Cécile Masson; Nathalie Boddaert; Marina Charbit; Stéphane Decramer; Robert Novo; Marie Alice Macher; Bruno Ranchin; Justine Bacchetta; Audrey Laurent; Sophie Collardeau-Frachon; Albertien M. van Eerde; Friedhelm Hildebrandt; Daniella Magen; Corinne Antignac; Herman van Tilbeurgh; Géraldine Mollet

doi:10.1038/s41467-019-11951-x

Defects in t⁶A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome

Christelle Arrondel, Sophia Missoury, Rozemarijn Snoek, Julie Patat, Giulia Menara, Bruno Collinet, Dominique Liger, Dominique Durand, Olivier Gribouval, Olivia Boyer, Laurine Buscara, Gaëlle Martin, Eduardo Machuca, Fabien Nevo, Ewen Lescop, Daniela A. Braun, Anne Claire Boschat, Sylvia Sanquer, Ida Chiara Guerrera, Patrick RevyMélanie Parisot, Cécile Masson, Nathalie Boddaert, Marina Charbit, Stéphane Decramer, Robert Novo, Marie Alice Macher, Bruno Ranchin, Justine Bacchetta, Audrey Laurent, Sophie Collardeau-Frachon, Albertien M. van Eerde, Friedhelm Hildebrandt, Daniella Magen, Corinne Antignac, Herman van Tilbeurgh, Géraldine Mollet^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

N⁶-threonyl-carbamoylation of adenosine 37 of ANN-type tRNAs (t⁶A) is a universal modification essential for translational accuracy and efficiency. The t⁶A pathway uses two sequentially acting enzymes, YRDC and OSGEP, the latter being a subunit of the multiprotein KEOPS complex. We recently identified mutations in genes encoding four out of the five KEOPS subunits in children with Galloway-Mowat syndrome (GAMOS), a clinically heterogeneous autosomal recessive disease characterized by early-onset steroid-resistant nephrotic syndrome and microcephaly. Here we show that mutations in YRDC cause an extremely severe form of GAMOS whereas mutations in GON7, encoding the fifth KEOPS subunit, lead to a milder form of the disease. The crystal structure of the GON7/LAGE3/OSGEP subcomplex shows that the intrinsically disordered GON7 protein becomes partially structured upon binding to LAGE3. The structure and cellular characterization of GON7 suggest its involvement in the cellular stability and quaternary arrangement of the KEOPS complex.

Original language	English
Article number	3967
Pages (from-to)	1-13
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11951-x
Publication status	Published - 3 Sept 2019

Keywords

Adenosine/analogs & derivatives
Child
Female
GTP-Binding Proteins/chemistry
Hernia, Hiatal/genetics
Humans
Intrinsically Disordered Proteins/genetics
Male
Microcephaly/genetics
Multiprotein Complexes/chemistry
Mutation
Nephrosis/genetics
Nuclear Proteins/chemistry
RNA, Transfer/genetics
RNA-Binding Proteins/chemistry

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Arrondel, C., Missoury, S., Snoek, R., Patat, J., Menara, G., Collinet, B., Liger, D., Durand, D., Gribouval, O., Boyer, O., Buscara, L., Martin, G., Machuca, E., Nevo, F., Lescop, E., Braun, D. A., Boschat, A. C., Sanquer, S., Guerrera, I. C., ... Mollet, G. (2019). Defects in t⁶A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome. Nature Communications, 10(1), 1-13. Article 3967. https://doi.org/10.1038/s41467-019-11951-x

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title = "Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome",

abstract = "N6-threonyl-carbamoylation of adenosine 37 of ANN-type tRNAs (t6A) is a universal modification essential for translational accuracy and efficiency. The t6A pathway uses two sequentially acting enzymes, YRDC and OSGEP, the latter being a subunit of the multiprotein KEOPS complex. We recently identified mutations in genes encoding four out of the five KEOPS subunits in children with Galloway-Mowat syndrome (GAMOS), a clinically heterogeneous autosomal recessive disease characterized by early-onset steroid-resistant nephrotic syndrome and microcephaly. Here we show that mutations in YRDC cause an extremely severe form of GAMOS whereas mutations in GON7, encoding the fifth KEOPS subunit, lead to a milder form of the disease. The crystal structure of the GON7/LAGE3/OSGEP subcomplex shows that the intrinsically disordered GON7 protein becomes partially structured upon binding to LAGE3. The structure and cellular characterization of GON7 suggest its involvement in the cellular stability and quaternary arrangement of the KEOPS complex.",

keywords = "Adenosine/analogs & derivatives, Child, Female, GTP-Binding Proteins/chemistry, Hernia, Hiatal/genetics, Humans, Intrinsically Disordered Proteins/genetics, Male, Microcephaly/genetics, Multiprotein Complexes/chemistry, Mutation, Nephrosis/genetics, Nuclear Proteins/chemistry, RNA, Transfer/genetics, RNA-Binding Proteins/chemistry",

author = "Christelle Arrondel and Sophia Missoury and Rozemarijn Snoek and Julie Patat and Giulia Menara and Bruno Collinet and Dominique Liger and Dominique Durand and Olivier Gribouval and Olivia Boyer and Laurine Buscara and Ga{\"e}lle Martin and Eduardo Machuca and Fabien Nevo and Ewen Lescop and Braun, {Daniela A.} and Boschat, {Anne Claire} and Sylvia Sanquer and Guerrera, {Ida Chiara} and Patrick Revy and M{\'e}lanie Parisot and C{\'e}cile Masson and Nathalie Boddaert and Marina Charbit and St{\'e}phane Decramer and Robert Novo and Macher, {Marie Alice} and Bruno Ranchin and Justine Bacchetta and Audrey Laurent and Sophie Collardeau-Frachon and {van Eerde}, {Albertien M.} and Friedhelm Hildebrandt and Daniella Magen and Corinne Antignac and {van Tilbeurgh}, Herman and G{\'e}raldine Mollet",

year = "2019",

month = sep,

day = "3",

doi = "10.1038/s41467-019-11951-x",

language = "English",

volume = "10",

pages = "1--13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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Arrondel, C, Missoury, S, Snoek, R, Patat, J, Menara, G, Collinet, B, Liger, D, Durand, D, Gribouval, O, Boyer, O, Buscara, L, Martin, G, Machuca, E, Nevo, F, Lescop, E, Braun, DA, Boschat, AC, Sanquer, S, Guerrera, IC, Revy, P, Parisot, M, Masson, C, Boddaert, N, Charbit, M, Decramer, S, Novo, R, Macher, MA, Ranchin, B, Bacchetta, J, Laurent, A, Collardeau-Frachon, S, van Eerde, AM, Hildebrandt, F, Magen, D, Antignac, C, van Tilbeurgh, H & Mollet, G 2019, 'Defects in t⁶A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome', Nature Communications, vol. 10, no. 1, 3967, pp. 1-13. https://doi.org/10.1038/s41467-019-11951-x

TY - JOUR

T1 - Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome

AU - Arrondel, Christelle

AU - Missoury, Sophia

AU - Snoek, Rozemarijn

AU - Patat, Julie

AU - Menara, Giulia

AU - Collinet, Bruno

AU - Liger, Dominique

AU - Durand, Dominique

AU - Gribouval, Olivier

AU - Boyer, Olivia

AU - Buscara, Laurine

AU - Martin, Gaëlle

AU - Machuca, Eduardo

AU - Nevo, Fabien

AU - Lescop, Ewen

AU - Braun, Daniela A.

AU - Boschat, Anne Claire

AU - Sanquer, Sylvia

AU - Guerrera, Ida Chiara

AU - Revy, Patrick

AU - Parisot, Mélanie

AU - Masson, Cécile

AU - Boddaert, Nathalie

AU - Charbit, Marina

AU - Decramer, Stéphane

AU - Novo, Robert

AU - Macher, Marie Alice

AU - Ranchin, Bruno

AU - Bacchetta, Justine

AU - Laurent, Audrey

AU - Collardeau-Frachon, Sophie

AU - van Eerde, Albertien M.

AU - Hildebrandt, Friedhelm

AU - Magen, Daniella

AU - Antignac, Corinne

AU - van Tilbeurgh, Herman

AU - Mollet, Géraldine

PY - 2019/9/3

Y1 - 2019/9/3

N2 - N6-threonyl-carbamoylation of adenosine 37 of ANN-type tRNAs (t6A) is a universal modification essential for translational accuracy and efficiency. The t6A pathway uses two sequentially acting enzymes, YRDC and OSGEP, the latter being a subunit of the multiprotein KEOPS complex. We recently identified mutations in genes encoding four out of the five KEOPS subunits in children with Galloway-Mowat syndrome (GAMOS), a clinically heterogeneous autosomal recessive disease characterized by early-onset steroid-resistant nephrotic syndrome and microcephaly. Here we show that mutations in YRDC cause an extremely severe form of GAMOS whereas mutations in GON7, encoding the fifth KEOPS subunit, lead to a milder form of the disease. The crystal structure of the GON7/LAGE3/OSGEP subcomplex shows that the intrinsically disordered GON7 protein becomes partially structured upon binding to LAGE3. The structure and cellular characterization of GON7 suggest its involvement in the cellular stability and quaternary arrangement of the KEOPS complex.

AB - N6-threonyl-carbamoylation of adenosine 37 of ANN-type tRNAs (t6A) is a universal modification essential for translational accuracy and efficiency. The t6A pathway uses two sequentially acting enzymes, YRDC and OSGEP, the latter being a subunit of the multiprotein KEOPS complex. We recently identified mutations in genes encoding four out of the five KEOPS subunits in children with Galloway-Mowat syndrome (GAMOS), a clinically heterogeneous autosomal recessive disease characterized by early-onset steroid-resistant nephrotic syndrome and microcephaly. Here we show that mutations in YRDC cause an extremely severe form of GAMOS whereas mutations in GON7, encoding the fifth KEOPS subunit, lead to a milder form of the disease. The crystal structure of the GON7/LAGE3/OSGEP subcomplex shows that the intrinsically disordered GON7 protein becomes partially structured upon binding to LAGE3. The structure and cellular characterization of GON7 suggest its involvement in the cellular stability and quaternary arrangement of the KEOPS complex.

KW - Adenosine/analogs & derivatives

KW - Child

KW - Female

KW - GTP-Binding Proteins/chemistry

KW - Hernia, Hiatal/genetics

KW - Humans

KW - Intrinsically Disordered Proteins/genetics

KW - Male

KW - Microcephaly/genetics

KW - Multiprotein Complexes/chemistry

KW - Mutation

KW - Nephrosis/genetics

KW - Nuclear Proteins/chemistry

KW - RNA, Transfer/genetics

KW - RNA-Binding Proteins/chemistry

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U2 - 10.1038/s41467-019-11951-x

DO - 10.1038/s41467-019-11951-x

M3 - Article

C2 - 31481669

AN - SCOPUS:85071756004

SN - 2041-1723

VL - 10

SP - 1

EP - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3967

ER -

Defects in t⁶A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome

Abstract

Keywords

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