Science Topics – 145
Defects in genes on the X chromosome contributes intellectual disability (ID) with X-linked intellectual disability (XLID) estimated to comprise 5~16% of all male ID patients. FTSJ1 is one of the candidate genes for XLID. However, the precise molecular functions of the protein encoded by FTSJ1 are unknown. Recently, Trm7, a homolog of FTSJ1 in Yeast was identified as a transfer RNA (tRNA) modification enzyme. Therefore, we formulated a hypothesis that FTSJ1 is involved in precise protein translation with tRNA modification and the defect underlies the molecular mechanism of XLID.
We generated Ftsj1 knockout (KO) mice. Among all tRNA species, steady-state level of tRNAPhe was selectively and significantly reduced in the Ftsj1 KO mouse brain, but not in other tissues. Furthermore, decoding at Phe codons was selectively impaired in the Ftsj1 KO brain, leading to a decrease in translation of genes related to synaptic activity and structure. The aberrant protein synthesis caused the electrophysiological and morphological abnormalities in both cortical and hippocampal neurons. Importantly, both spatial and fear memories, which mirrors the symptoms of human patients were impaired in Ftsj1 KO mice.
Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability.
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 and F.-Y. Wei
Science Advances 7(13): eabf3072, 2021.
＜Figure Legends＞
A schema summarizing the molecular mechanism on X-linked intellectual disability by disfunction of FTSJ1.
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Japan
Department of Modomics Biology and Medicine, Institute of Development, Aging and Cancer, Tohoku University, Japan