Ribosome depurination by ricin leads to inhibition of endoplasmic reticulum stress-induced HAC1 mRNA splicing on the ribosome.

ABSTRACT: Ricin undergoes retrograde transport to the endoplasmic reticulum (ER), and ricin toxin A chain (RTA) enters the cytosol from the ER. Previous reports indicated that RTA inhibits activation of the unfolded protein response (UPR) in yeast and in mammalian cells. Both precursor (preRTA) and mature form of RTA (mRTA) inhibited splicing of HAC1^u (u for uninduced) mRNA, suggesting that UPR inhibition occurred on the cytosolic face of the ER. Here, we examined the role of ribosome binding and depurination activity on inhibition of the UPR using mRTA mutants. An active-site mutant with very low depurination activity, which bound ribosomes as WT RTA, did not inhibit HAC1^u mRNA splicing. A ribosome-binding mutant, which showed reduced binding to ribosomes

SUBMITTER: Pierce M 

PROVIDER: S-EPMC6879324 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature