@article{3641, keywords = {Protein Biosynthesis, Transcription, Genetic, RNA, Messenger, Humans, Immunity, Innate, Endoribonucleases, RNA, Double-Stranded, RNA Stability, A549 Cells}, author = {Sneha Rath and Eliza Prangley and Jesse Donovan and Kaitlin Demarest and Ned Wingreen and Yigal Meir and Alexei Korennykh}, title = {Concerted 2-5A-Mediated mRNA Decay and Transcription Reprogram Protein Synthesis in the dsRNA Response.}, abstract = {

Viral and endogenous double-stranded RNA (dsRNA) is a potent trigger for programmed RNA degradation by the 2-5A/RNase L complex in cells of all mammals. This 2-5A-mediated decay (2-5AMD) is a conserved stress response switching global protein synthesis from homeostasis to production of interferons (IFNs). To understand this mechanism, we examined 2-5AMD in human cells and found that it triggers polysome collapse characteristic of inhibited translation initiation. We determined that translation initiation complexes and ribosomes purified from translation-arrested cells remain functional. However, spike-in RNA sequencing (RNA-seq) revealed cell-wide decay of basal mRNAs accompanied by rapid accumulation of mRNAs encoding innate immune proteins. Our data attribute this 2-5AMD evasion to better stability of defense mRNAs and positive feedback in the IFN response amplified by RNase L-resistant molecules. We conclude that 2-5AMD and transcription act in concert to refill mammalian cells with defense mRNAs, thereby "prioritizing" the synthesis of innate immune proteins.

}, year = {2019}, journal = {Mol Cell}, volume = {75}, pages = {1218-1228.e6}, month = {2019 Sep 19}, issn = {1097-4164}, doi = {10.1016/j.molcel.2019.07.027}, language = {eng}, }