Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 37, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2104577118|1of7
Keywords
diphthamide; translation; frameshifting; TOR signaling
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Diphthamide, a modification unique to translation elongation factor 2 (EF2), suppresses -1 frameshifting in translation and affects the TORC1/mTORC1 signaling pathway. In yeast, diphthamide deficiency inhibits the translation of TORC1-activating proteins.
Diphthamide, a modification found only on translation elongation factor 2 (EF2), was proposed to suppress -1 frameshifting in translation. Although diphthamide is conserved among all eukaryotes, exactly what proteins are affected by diphthamide deletion is not clear in cells. Through genome-wide profiling for a potential -1 frameshifting site, we identified that the target of rapamycin complex 1 (TORC1)/mammalian TORC1 (mTORC1) signaling pathway is affected by deletion of diphthamide. Diphthamide deficiency in yeast suppresses the translation of TORC1-activating proteins Vam6 and Rtc1. Interestingly, TORC1 signaling also promotes diphthamide biosynthesis, suggesting that diphthamide forms a positive feedback loop to promote translation under nutrient-rich conditions. Our results provide an explanation for why diphthamide is evolutionarily conserved and why diphthamide deletion can cause severe developmental defects.
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