Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers

• DOI: 10.1073/pnas.1510077112
• Publication Date: 2015-06-30T02:55:30Z
• Authors: Shozo Honda; Phillipe Loher; Megumi Shigematsu; Juan P. Palazzo; Ryusuke Suzuki; Issei Imoto; Isidore Rigoutsos; Yohei Kirino
• Keywords: Male; 0301 basic medicine; 570; Molecular Sequence Data; 610; Breast Neoplasms; Medical Biochemistry; Hydroxylation; Real-Time Polymerase Chain Reaction; Models, Biological; Phosphates; sex hormone; 03 medical and health sciences; breast cancer; RNA, Transfer; Cell Line, Tumor; Medicine and Health Sciences; Animals; Humans; Amino Acids; Gonadal Steroid Hormones; tRNA; Cell Proliferation; tRNA half; Base Sequence; Prostatic Neoplasms; Epithelial Cells; prostate cancer; Bombyx; 3. Good health; Gene Knockdown Techniques; Female

Significance Although transfer RNAs (tRNAs) are best known as adapter molecules essential for translation, recent biochemical and computational evidence has led to a previously unexpected conceptual consensus that tRNAs are not always end products but can further serve as a source of small functional RNAs. Here we report that a novel type of tRNA-derived small RNA, termed SHOT-RNAs, are specifically and abundantly expressed in sex hormone-dependent breast and prostate cancers. SHOT-RNAs are produced from aminoacylated mature tRNAs by angiogenin-mediated cleavage of the anticodon loop, which is promoted by sex hormones and their receptors. We identified the complete repertoire of SHOT-RNAs, and also found their functional significance in cell proliferation. These results have unveiled a novel tRNA-engaged pathway in tumorigenesis.