5'-tiRNA-Gln inhibits hepatocellular carcinoma progression by repressing translation through the interaction with eukaryotic initiation factor 4A-I / 医学前沿

tRNA-derived small RNAs (tsRNAs) are novel non-coding RNAs that are involved in the occurrence and progression of diverse diseases. However, their exact presence and function in hepatocellular carcinoma (HCC) remain unclear. Here, differentially expressed tsRNAs in HCC were profiled. A novel tsRNA, tRNAGln-TTG derived 5'-tiRNA-Gln, is significantly downregulated, and its expression level is correlated with progression in patients. In HCC cells, 5'-tiRNA-Gln overexpression impaired the proliferation, migration, and invasion in vitro and in vivo, while 5'-tiRNA-Gln knockdown yielded opposite results. 5'-tiRNA-Gln exerted its function by binding eukaryotic initiation factor 4A-I (EIF4A1), which unwinds complex RNA secondary structures during translation initiation, causing the partial inhibition of translation. The suppressed downregulated proteins include ARAF, MEK1/2 and STAT3, causing the impaired signaling pathway related to HCC progression. Furthermore, based on the construction of a mutant 5'-tiRNA-Gln, the sequence of forming intramolecular G-quadruplex structure is crucial for 5'-tiRNA-Gln to strongly bind EIF4A1 and repress translation. Clinically, 5'-tiRNA-Gln expression level is negatively correlated with ARAF, MEK1/2, and STAT3 in HCC tissues. Collectively, these findings reveal that 5'-tiRJNA-Gln interacts with EIF4A1 to reduce related mRNA binding through the intramolecular G-quadruplex structure, and this process partially inhibits translation and HCC progression.

Identification of tRNA-Derived Fragments and Their Regulatory Mechanisms on Target Molecules / 中国生物化学与分子生物学报

With the development of sequencing technology and in-depth research on tRNA-derived small molecules (tsRNAs)‚ more and more tRNAs and their functions have been identified in various species. tsRNAs can be divided into tRNA-derived fragment (tRF) and tRNA-derived stress-induced RNA (tiRNA) according to different cleavage sites. And we will focus on tRF‚ which is a kind of non-coding RNA with regulatory function. To deepen the research of tRF‚ a large number of tRF identification methods based on sequencing data and corresponding databases are being constructed in recent years. The former mainly includes the method of Telonis et al. and tDRmapper‚ while the latter mainly includes tRFdb‚ tRF2Cancer and MINTbase. At the same time‚ both provide a more effective tool for the in-depth research of tRF. The regulation mechanisms of tRF are also being illustrated in many studies. tRF mainly regulates the expression of RNA‚ DNA and proteins in a miRNA-like manner. With further investigations‚ researchers have found that tRF also plays a specific regulatory role in various biological processes of human diseases‚ suggesting its role as a potential biomarker. Herein we mainly summarize the identification methods‚ databases‚ regulation mechanisms of tRF and its role in human diseases.