論文

国際誌
2021年3月

Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability.

Science advances
  • Y Nagayoshi
  • T Chujo
  • S Hirata
  • H Nakatsuka
  • C-W Chen
  • M Takakura
  • K Miyauchi
  • Y Ikeuchi
  • B C Carlyle
  • R R Kitchen
  • T Suzuki
  • F Katsuoka
  • M Yamamoto
  • Y Goto
  • M Tanaka
  • K Natsume
  • A C Nairn
  • T Suzuki
  • K Tomizawa
  • F-Y Wei
  • 全て表示

7
13
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1126/sciadv.abf3072

FtsJ RNA 2'-O-methyltransferase 1 (FTSJ1) gene has been implicated in X-linked intellectual disability (XLID), but the molecular pathogenesis is unknown. We show that Ftsj1 is responsible for 2'-O-methylation of 11 species of cytosolic transfer RNAs (tRNAs) at the anticodon region, and these modifications are abolished in Ftsj1 knockout (KO) mice and XLID patient-derived cells. Loss of 2'-O-methylation in Ftsj1 KO mouse selectively reduced the steady-state level of tRNAPhe in the brain, resulting in a slow decoding at Phe codons. Ribosome profiling showed that translation efficiency is significantly reduced in a subset of genes that need to be efficiently translated to support synaptic organization and functions. Ftsj1 KO mice display immature synaptic morphology and aberrant synaptic plasticity, which are associated with anxiety-like and memory deficits. The data illuminate a fundamental role of tRNA modification in the brain through regulation of translation efficiency and provide mechanistic insights into FTSJ1-related XLID.

リンク情報
DOI
https://doi.org/10.1126/sciadv.abf3072
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33771871
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997516
ID情報
  • DOI : 10.1126/sciadv.abf3072
  • PubMed ID : 33771871
  • PubMed Central 記事ID : PMC7997516

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