Rapid RNase L-driven Arrest of Protein Synthesis in the DsRNA Response Without Degradation of Translation Machinery

Overview

Journal RNA

Specialty Molecular Biology

Date 2017 Aug 16

PMID 28808124

Citations 85

Authors

Jesse Donovan

Sneha Rath

David Kolet-Mandrikov

Alexei Korennykh

Affiliations

Soon will be listed here.

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.

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