RT Journal Article
SR Electronic
T1 RNase L reprograms translation by widespread mRNA turnover escaped by antiviral mRNAs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 486530
DO 10.1101/486530
A1 James M Burke
A1 Stephanie L Moon
A1 Evan T Lester
A1 Tyler Matheny
A1 Roy Parker
YR 2018
UL http://biorxiv.org/content/early/2018/12/04/486530.abstract
AB In response to foreign and endogenous double-stranded RNA (dsRNA), protein kinase R (PKR) and ribonuclease L (RNase L) reprogram translation in mammalian cells. PKR inhibits translation initiation through eIF2α phosphorylation, which triggers stress granule (SG) formation and promotes translation of stress responsive mRNAs. The mechanisms of RNase L-driven translation repression, its contribution to SG assembly, and its regulation of dsRNA stress-induced mRNAs are unknown. We demonstrate that RNase L drives translational shut-off in response to dsRNA by promoting widespread turnover of mRNAs. This alters stress granule assembly and reprograms translation by only allowing for the translation of mRNAs resistant to RNase L degradation, including numerous antiviral mRNAs such as IFN-β. Individual cells differentially activate dsRNA responses revealing variation that can affect cellular outcomes. This identifies bulk mRNA degradation and the resistance of antiviral mRNAs as the mechanism by which RNaseL reprograms translation in response to dsRNA.