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

Author(s): Donovan, Jesse; Rath, Sneha; Kolet-Mandrikov, David; Korennykh, Alexei

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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.
Publication Date: Nov-2017
Citation: Donovan, Jesse, Rath, Sneha, Kolet-Mandrikov, David, Korennykh, Alexei. (2017). Rapid RNase L-driven arrest of protein synthesis in the dsRNA response without degradation of translation machinery.. RNA, 23 (11), 1660 - 1671. doi:10.1261/rna.062000.117
DOI: doi:10.1261/rna.062000.117
ISSN: 1355-8382
EISSN: 1469-9001
Pages: 1660 - 1671
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: RNA
Version: Final published version. This is an open access article.



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