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/LA

SUBMITTER: Arrondel C 

PROVIDER: S-EPMC6722078 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature