TY - JOUR
T1 - Rapid RNase L–driven arrest of protein synthesis in the dsRNA response without degradation of translation machinery
AU - Donovan, Jesse
AU - Rath, Sneha
AU - Kolet-Mandrikov, David
AU - Korennykh, Alexei
PY - 2017/11
Y1 - 2017/11
N2 - 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.
AB - 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.
KW - RNase L
KW - Signaling
KW - TRNA
KW - Translation
KW - Y-RNA
UR - http://www.scopus.com/inward/record.url?scp=85031946542&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85031946542&partnerID=8YFLogxK
U2 - 10.1261/rna.062000.117
DO - 10.1261/rna.062000.117
M3 - Article
C2 - 28808124
AN - SCOPUS:85031946542
VL - 23
SP - 1660
EP - 1671
JO - RNA
JF - RNA
SN - 1355-8382
IS - 11
ER -