Ribosomal protein mRNAs are primary targets of regulation in RNase-L-induced senescence
Research output: Contribution to journal › Journal article › Research › peer-review
The endoribonuclease RNase-L requires 2',5'-linked oligoadenylates for activation, and mediates antiviral and antiproliferative activities. We previously determined that RNase-L activation induces senescence; to determine potential mechanisms underlying this activity, we used microarrays to identify RNase-L-regulated mRNAs. RNase-L activation affected affected a finite number of transcripts, and thus does not lead to a global change in mRNA turnover. The largest classes of downregulated transcripts, that represent candidate RNase-L substrates, function in protein biosynthesis, metabolism and proliferation. Among these, mRNAs encoding ribosomal proteins (RPs) were particularly enriched. The reduced levels of four RP mRNAs corresponded with a decrease in their half lives and a physical association with an RNase-L-ribonucleoprotein (RNP) complex in cells, suggesting that they represent authentic RNase-L substrates. Sequence and structural analysis of the downregulated mRNAs identified a putative RNase-L target motif that was used for the in silico identification of a novel RNase-L-RNP-interacting transcript. The downregulation of RP mRNAs corresponded with a marked reduction in protein translation, consistent with the roles of RP proteins in ribosome function. Our data support a model in which the RNase-L-mediated degradation of RP mRNAs inhibits translation, and may contribute to its antiproliferative, senescence inducing and tumor suppressor activities.
Original language | English |
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Journal | RNA Biology |
Volume | 6 |
Issue number | 3 |
Pages (from-to) | 305-15 |
Number of pages | 11 |
Publication status | Published - 2009 |
Externally published | Yes |
- Animals, Base Sequence, Cell Aging, Cell Line, Down-Regulation, Endoribonucleases, Enzyme Activation, Gene Expression Profiling, Mice, Mice, Knockout, Nucleic Acid Conformation, Protein Binding, RNA, Messenger, Ribosomal Proteins
Research areas
ID: 97139944