Dr. Goodarzi and others from Rockefeller University recently published their research in Cell describing a novel class of tRFs derived from tRNAGlu, tRNAAsp, tRNAGly, and tRNATyr that, upon induction, suppress the stability of multiple oncogenic transcripts in breast cancer cells by displacing their 3′ untranslated regions (UTRs) from the RNA-binding protein YBX1. Using the NEXTflex™ Small RNA Sequencing Kit v2 to measure small RNA levels under normal and hypoxic stress conditions, they identified a group of tRFs that were upregulated under hypoxia in breast cancer cells as well as in non-transformed mammary epithelial cells.
Goodarzi and others also found that this mode of post-transcriptional silencing is sequence specific, as these fragments all share a common motif that matches the YBX1 recognition sequence. Loss-of-function and gain-of-function studies, using anti-sense locked-nucleic acids (LNAs) and synthetic RNA mimetics, respectively, revealed that these fragments suppress growth under serum-starvation, cancer cell invasion, and metastasis by breast cancer cells. Highly metastatic cells evade this tumor-suppressive pathway by attenuating the induction of these tRFs. Their findings revealed a tumor-suppressive role for specific tRNA-derived fragments and describe a molecular mechanism for their action. This transcript displacement-based mechanism may generalize to other tRNA, ribosomal-RNA, and sno-RNA fragments.
Goodarzi, H., et al. (2015) Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement. Cell. 161:4, p790–802.