TY - JOUR
T1 - Oxidation and alkylation stresses activate ribosome-quality control
AU - Yan, Liewei L.
AU - Simms, Carrie L.
AU - McLoughlin, Fionn
AU - Vierstra, Richard D.
AU - Zaher, Hani S.
N1 - Funding Information:
The authors thank Roy Parker for sharing the Dcp2-GFP plasmid and Ray Deshaies for supplying the cdc48 temperature-sensitive strains. The authors are grateful for Nima Mosammaparast and Bob Kranz for their comments on earlier versions of the manuscript, and members of the Zaher Laboratory for useful discussion. This work was supported by a grant from the National Institute of General Medical Sciences of the NIH (R01GM112641 to H.S.Z.).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Oxidation and alkylation of nucleobases are known to disrupt their base-pairing properties within RNA. It is, however, unclear whether organisms have evolved general mechanism(s) to deal with this damage. Here we show that the mRNA-surveillance pathway of no-go decay and the associated ribosome-quality control are activated in response to nucleobase alkylation and oxidation. Our findings reveal that these processes are important for clearing chemically modified mRNA and the resulting aberrant-protein products. In the absence of Xrn1, the level of damaged mRNA significantly increases. Furthermore, deletion of LTN1 results in the accumulation of protein aggregates in the presence of oxidizing and alkylating agents. This accumulation is accompanied by Hel2-dependent regulatory ubiquitylation of ribosomal proteins. Collectively, our data highlight the burden of chemically damaged mRNA on cellular homeostasis and suggest that organisms evolved mechanisms to counter their accumulation.
AB - Oxidation and alkylation of nucleobases are known to disrupt their base-pairing properties within RNA. It is, however, unclear whether organisms have evolved general mechanism(s) to deal with this damage. Here we show that the mRNA-surveillance pathway of no-go decay and the associated ribosome-quality control are activated in response to nucleobase alkylation and oxidation. Our findings reveal that these processes are important for clearing chemically modified mRNA and the resulting aberrant-protein products. In the absence of Xrn1, the level of damaged mRNA significantly increases. Furthermore, deletion of LTN1 results in the accumulation of protein aggregates in the presence of oxidizing and alkylating agents. This accumulation is accompanied by Hel2-dependent regulatory ubiquitylation of ribosomal proteins. Collectively, our data highlight the burden of chemically damaged mRNA on cellular homeostasis and suggest that organisms evolved mechanisms to counter their accumulation.
UR - http://www.scopus.com/inward/record.url?scp=85076292450&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-13579-3
DO - 10.1038/s41467-019-13579-3
M3 - Article
C2 - 31819057
AN - SCOPUS:85076292450
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5611
ER -