@article{aa1ff5cb70e74921a75389b7cf968041,
title = "Rapid RNase L–driven arrest of protein synthesis in the dsRNA response without degradation of translation machinery",
abstract = "Mammalian cells respond to double-stranded RNA (dsRNA) by activating a translation-inhibiting endoribonuclease, RNase L. Consensus in the field indicates that RNase L arrests protein synthesis by degrading ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs). However, here we provide evidence for a different and far more efficient mechanism. By sequencing abundant RNA fragments generated by RNase L in human cells, we identify site-specific cleavage of two groups of noncoding RNAs: Y-RNAs, whose function is poorly understood, and cytosolic tRNAs, which are essential for translation. Quantitative analysis of human RNA cleavage versus nascent protein synthesis in lung carcinoma cells shows that RNase L stops global translation when tRNAs, as well as rRNAs and mRNAs, are still intact. Therefore, RNase L does not have to degrade the translation machinery to stop protein synthesis. Our data point to a rapid mechanism that transforms a subtle RNA cleavage into a cell-wide translation arrest.",
keywords = "RNase L, Signaling, TRNA, Translation, Y-RNA",
author = "Jesse Donovan and Sneha Rath and David Kolet-Mandrikov and Alexei Korennykh",
note = "Funding Information: We thank Professor Susan Weiss and Yize (Henry) Li (University of Pennsylvania School of Medicine) for the gift of A546 WT and RNase L−/− cells (Li et al. 2016). We thank Dr. Marcin Grabowicz and Professor Thomas Silhavy (Princeton University) for the gift of E. coli strains, and Professor Elizabeth Gavis for sharing instrumentation. We thank Professor Andrei Korostelev for help in designing ribozyme constructs and comments on the manuscript, and Professor Pavel Ivanov (Harvard Medical School) for important discussions about tRNA cleavage. We are grateful to Dr. Wei Wang and the staff of Princeton University{\textquoteright}s sequencing core facility for help with RNA sequencing. We thank members of the Korennykh laboratory for reading the manuscript and providing valuable comments. We are grateful to Professor Roy Parker for making valuable suggestions during review. This study was funded by Princeton University, National Institutes of Health grants 5T32GM007388 and F99 CA212468-01 (to S.R.), National Institutes of Health grant 1R01GM110161-01 (to A.K.), Sidney Kimmel Foundation grant AWD1004002 (to A.K.), and Burroughs Wellcome Foundation Grant 1013579 (to A.K.). Publisher Copyright: {\textcopyright} 2017 Donovan et al.",
year = "2017",
month = nov,
doi = "10.1261/rna.062000.117",
language = "English (US)",
volume = "23",
pages = "1660--1671",
journal = "RNA",
issn = "1355-8382",
publisher = "Cold Spring Harbor Laboratory Press",
number = "11",
}