A Novel tRNA-mediated Pathway in Tumorigenesis

Cancer 2 Transfer RNAs (tRNAs) are best known as adaptor molecules in protein synthesis, but recent evidence suggests that they can also serve as a source of small functional RNAs. 
Scientists have. identifiedtRNA halves, termed SHOT-RNAs, that are derived from mature tRNAs and are constitutively expressed in sex hormone-dependent breast and prostate cancer cells in culture and in cancer patient tissues. 
Suppressing the expression of the enzyme angiogenin by RNA interference reduced SHOT-RNA levels, suggesting that angiogenin cleaves mature tRNAs to produce SHOT-RNAs. 
The authors determined that eight tRNAs were the source of nearly all SHOT-RNAs, and were formed by cleavage of the mature tRNA at nucleotide position 32–34. 
Suppression of estrogen receptor or androgen receptor expression also reduced SHOT-RNA levels, as did culturing cells in hormone-free medium, whereas addition of sex hormones to the culture medium increased SHOT-RNA levels. The finding suggests that sex hormones and their receptors promote formation of SHOT-RNAs. 
Finally, suppressing expression of SHOT-RNAs reduced the rate of cell growth, suggesting that SHOT-RNAs are required for cell proliferation. According to the authors, a tRNA-mediated pathway might play a role in tumorigenesis of hormone-dependent cancers, and SHOT-RNAs might represent possible therapeutic targets.
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