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首页> 外文期刊>EMBO reports >Intellectual disability-associated geneftsj1is responsible for 2 '-O-methylation of specific tRNAs
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Intellectual disability-associated geneftsj1is responsible for 2 '-O-methylation of specific tRNAs

机译：Intellectual disability-associated geneftsj1is responsible for 2 '-O-methylation of specific tRNAs

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摘要

tRNA modifications at the anti-codon loop are critical for accurate decoding. FTSJ1 was hypothesized to be a human tRNA 2 '-O-methyltransferase. tRNA(Phe)(GAA) from intellectual disability patients with mutations inftsj1lacks 2 '-O-methylation at C32 and G34 (Cm32 and Gm34). However, the catalytic activity, RNA substrates, and pathogenic mechanism of FTSJ1 remain unknown, owing, in part, to the difficulty in reconstituting enzymatic activityin vitro. Here, we identify an interacting protein of FTSJ1, WDR6. For the first time, we reconstitute the 2 '-O-methylation activity of the FTSJ1-WDR6 complexin vitro, which occurs at position 34 of specific tRNAs with m(1)G37 as a prerequisite. We find that modifications at positions 32, 34, and 37 are interdependent and occur in a hierarchical orderin vivo. We also show that the translation efficiency of the UUU codon, but not the UUC codon decoded by tRNA(Phe)(GAA), is reduced inftsj1knockout cells. Bioinformatics analysis reveals that almost 40% of the high TTT-biased genes are related to brain/nervous functions. Our data potentially enhance our understanding of the relationship between FTSJ1 and nervous system development.

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