Fig. 4: RNA-binding protein-associated regulation.
From: Emerging roles of tRNA-derived small RNAs in cancer biology
a Suppression: tsRNAs act as decoys. Internal tsRNA (i-tRF) binds to Y-box binding protein 1 (YB-1 or YBX1) and interferes with the interaction of YBX1 with several oncogenic transcripts. This reduces the stability of oncogenic transcripts and suppresses the metastasis of breast cancer cells. b Stabilization: tsRNAs induce nucleolin oligomerization. The CysGCA5′tRNA half binds to nucleolin and enhances the interaction of nucleolin with platelet-activating factor acetylhydrolase 1 beta 1 (Pafah1b1) and methylenehydrofolate dehydrogenase 1 like (Mthfd1l) transcripts. This induces nucleolin oligomerization, which protects these transcripts from exonucleolytic degradation and increases their stability, thereby increasing metastasis. c Stabilization: tsRNAs induce protein translocation. The 33-nt-GlyGCC 5′tRNA half binds to RBM17 and promotes its translocation to the nucleus. Stabilized RBM17 in the nucleus induces alternative splicing of MAP4K4 mRNA, increasing papillary thyroid cancer (PTC) cell proliferation and metastasis. d Inhibition of apoptosis: tsRNAs act as competitors. The binding of cytochrome c (cyt c) to the caspase activator Apaf-1 induces apoptosis. The 5′tRNA half binds to cyt c and interferes with the interaction between cyt c and Apaf-1. This prevents apoptosome formation and inhibits apoptosis.
