Rapid RNase L–driven arrest of protein synthesis in the dsRNA response without degradation of translation machinery

Jesse Donovan, Sneha Rath, David Kolet-Mandrikov, Alexei Korennykh

Research output: Contribution to journalArticle

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1660-1671
Number of pages12
JournalRNA
Volume23
Issue number11
DOIs
StatePublished - Nov 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology

Keywords

  • RNase L
  • Signaling
  • TRNA
  • Translation
  • Y-RNA

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