Potential physiological roles of the 31/32-nucleotide Y4-RNA fragment in human plasma

The 31- and 32-nt 5'-fragments of Y4-RNA (Y4RNAfr) exist abundantly in human plasma. The Y4RNAfr can function as 5'-half-tRNA-type sgRNA for tRNase Z^L, although we do not know yet what its physiological roles are and what cellular RNAs are its genuine targets. In this paper, we analyzed the effects of the Y4RNAfr on cell viability and transcriptomes using HL60, RPMI-8226, and HEK293 cells, and Y4RNAfr-binding RNAs in A549 cells. Although the Y4RNAfr hardly affected the viability of HL60, RPMI-8226, and HEK293 cells, it significantly affected their transcriptome. The DAVID analysis for > 2-fold upregulated and downregulated genes suggested that the Y4RNAfr may affect various KEGG pathways. We obtained 108 Y4RNAfr-binding RNAs in A549 cells, searched potential secondary structures of complexes between theY4RNAfr and its binding RNAs for the pre-tRNA-like structure, and found many such structures. One of the five best fitted structures was for the MKI67 mRNA, suggesting that the Y4RNAfr can decrease the cellular MKI67 level through guiding the cleavage of the MKI67 mRNA by tRNase Z^L. This may be one of the underlying mechanisms for the reported observation that the Y4RNAfr suppresses the proliferation of A549 cells.