TY - JOUR
T1 - Roles of Dom34:Hbs1 in Nonstop Protein Clearance from Translocators for Normal Organelle Protein Influx
AU - Izawa, Toshiaki
AU - Tsuboi, Tatsuhisa
AU - Kuroha, Kazushige
AU - Inada, Toshifumi
AU - Nishikawa, Shuh ichi
AU - Endo, Toshiya
N1 - Funding Information:
We thank J. Brodsky (University of Pittsburgh) for anti-Sec61 antibodies, A. Nakano (University of Tokyo) for anti-pαF antibodies, and the members of the Endo laboratory for discussions and comments. We acknowledge support of this work by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT).
PY - 2012/9/27
Y1 - 2012/9/27
N2 - Because messenger RNAs without a stop codon (nonstop mRNAs) generate stalled ribosomes, cells have developed a mechanism allowing degradation of nonstop mRNAs and their translation products (nonstop proteins) in the cytosol. Here, we observe the fate of nonstop proteins destined for organelles such as the endoplasmic reticulum (ER) and mitochondria. Nonstop mRNAs for secretory-pathway proteins in yeast generate nonstop proteins that become stuck in the translocator, the Sec61 complex, in the ER membrane. These stuck nonstop secretory proteins avoid proteasomal degradation in the cytosol, but are instead released into the ER lumen through stalled ribosome and translocator channels by Dom34:Hbs1. We also found that nonstop mitochondrial proteins are cleared from the mitochondrial translocator, the TOM40 complex, by Dom34:Hbs1. Clearance of stuck nonstop proteins from organellar translocator channels is crucial for normal protein influx into organelles and for normal cell growth, especially when nonstop mRNA decay does not function efficiently
AB - Because messenger RNAs without a stop codon (nonstop mRNAs) generate stalled ribosomes, cells have developed a mechanism allowing degradation of nonstop mRNAs and their translation products (nonstop proteins) in the cytosol. Here, we observe the fate of nonstop proteins destined for organelles such as the endoplasmic reticulum (ER) and mitochondria. Nonstop mRNAs for secretory-pathway proteins in yeast generate nonstop proteins that become stuck in the translocator, the Sec61 complex, in the ER membrane. These stuck nonstop secretory proteins avoid proteasomal degradation in the cytosol, but are instead released into the ER lumen through stalled ribosome and translocator channels by Dom34:Hbs1. We also found that nonstop mitochondrial proteins are cleared from the mitochondrial translocator, the TOM40 complex, by Dom34:Hbs1. Clearance of stuck nonstop proteins from organellar translocator channels is crucial for normal protein influx into organelles and for normal cell growth, especially when nonstop mRNA decay does not function efficiently
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U2 - 10.1016/j.celrep.2012.08.010
DO - 10.1016/j.celrep.2012.08.010
M3 - Article
C2 - 22981232
AN - SCOPUS:84866931539
VL - 2
SP - 447
EP - 453
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 3
ER -