Open AccessDiphthamide promotes TOR signaling by increasing the translation of proteins in the TORC1 pathway
Author(s) -
Yugang Zhang,
Zhewang Lin,
Julia Zhu,
Miao Wang,
Hening Lin
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2104577118
Subject(s) - biology , translation (biology) , genetics , microbiology and biotechnology , gene , messenger rna
Significance Diphthamide is a posttranslational modification that has been known since the 1970s. It is conserved in all eukaryotic cells, and its biosynthesis requires at least seven proteins. However, its exact biological function has remained unclear. Our results demonstrate that diphthamide promotes target of rapamycin (TOR) signaling by promoting the translation of two proteins in the target of rapamycin complex 1 (TORC1) pathway that contain slippery sequences in their messenger RNA (mRNA). Our finding explained why diphthamide is evolutionarily conserved and why it is crucial in animal development. Our results also suggest that regulating the translation of slippery sequences by diphthamide could be a widely used mechanism to tune translation in eukaryotes, which is different from the recoding hypothesis.