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Genome-wide Identification and Quantitative Analysis of Cleaved tRNA Fragments Induced by Cellular Stress
- Source :
- Journal of Biological Chemistry. 287:42708-42725
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Certain stress conditions can induce cleavage of tRNAs around the anticodon loop via the use of the ribonuclease angiogenin. The cellular factors that regulate tRNA cleavage are not well known. In this study we used normal and eIF2α phosphorylation-deficient mouse embryonic fibroblasts and applied a microarray-based methodology to identify and compare tRNA cleavage patterns in response to hypertonic stress, oxidative stress (arsenite), and treatment with recombinant angiogenin. In all three scenarios mouse embryonic fibroblasts deficient in eIF2α phosphorylation showed a higher accumulation of tRNA fragments including those derived from initiator-tRNA(Met). We have shown that tRNA cleavage is regulated by the availability of angiogenin, its substrate (tRNA), the levels of the angiogenin inhibitor RNH1, and the rates of protein synthesis. These conclusions are supported by the following findings: (i) exogenous treatment with angiogenin or knockdown of RNH1 increased tRNA cleavage; (ii) tRNA fragment accumulation was higher during oxidative stress than hypertonic stress, in agreement with a dramatic decrease of RNH1 levels during oxidative stress; and (iii) a positive correlation was observed between angiogenin-mediated tRNA cleavage and global protein synthesis rates. Identification of the stress-specific tRNA cleavage mechanisms and patterns will provide insights into the role of tRNA fragments in signaling pathways and stress-related disorders.
- Subjects :
- Angiogenin
Arsenites
Eukaryotic Initiation Factor-2
Hypertonic Solutions
Cleavage (embryo)
Biochemistry
Recombinant Angiogenin
Substrate Specificity
Mice
RNA, Transfer
Stress, Physiological
Anticodon
Protein biosynthesis
Animals
RNA, Messenger
Ribonuclease
Phosphorylation
Molecular Biology
Oligonucleotide Array Sequence Analysis
Cell Nucleus
Genome
Base Sequence
biology
RNA
Ribonuclease, Pancreatic
Cell Biology
stomatognathic diseases
Oxidative Stress
Gene Knockdown Techniques
Protein Biosynthesis
Transfer RNA
biology.protein
Nucleic Acid Conformation
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 287
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....5b1885e5890043da9c679d9cc481a236