Potential small guide RNAs for tRNase ZL from human plasma, peripheral blood mononuclear cells, and cultured cell lines

PLoS One. 2015 Mar 2;10(3):e0118631. doi: 10.1371/journal.pone.0118631. eCollection 2015.


Several pieces of evidence suggest that small RNA degradation products together with tRNase ZL appear to form another layer of the whole gene regulatory network. The degraded RNA such as a 5'-half-tRNA and an rRNA fragment function as small guide RNA (sgRNA) to guide the enzyme to target RNA. We were curious whether there exist RNAs in plasma that can function as sgRNAs for tRNase ZL, whether these RNAs are working as signaling molecules between cells to fulfill physiological roles, and whether there are any differences in plasma sgRNA species and levels between normal and pathological conditions. Here, we analyzed small plasma RNAs from three healthy persons and three multiple myeloma patients for potential sgRNAs by deep sequencing. We also examined small RNAs from peripheral blood mononuclear cells (PBMC) of three healthy persons and three myeloma patients and from various cultured human cell lines for sgRNAs. We found that read-number distribution patterns of plasma and PBMC RNAs differ between persons in the range of 5-40 nt and that there are many RNA species that exist significantly more or less abundantly in the plasma or PBMC of the myeloma patients than those of the healthy persons. Furthermore, we found that there are many potential sgRNAs in the 5-40-nt RNAs and that, among them, a 31-nt RNA fragment derived from 94-nt Y4-RNA, which can function as a 5'-half-tRNA-type sgRNA, is overwhelmingly abundant in the plasma of 2/3 of the examinees. These observations suggest that the gene regulatory network via tRNase ZL and sgRNA may be extended intercellularly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cells, Cultured
  • Endoribonucleases / blood
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Jurkat Cells
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism*
  • Multiple Myeloma / blood
  • Multiple Myeloma / pathology
  • Nucleic Acid Conformation
  • RNA / analysis
  • RNA / blood
  • RNA / isolation & purification
  • RNA, Guide, Kinetoplastida / analysis
  • RNA, Guide, Kinetoplastida / blood*
  • Sequence Analysis, RNA


  • RNA, Guide
  • RNA
  • Endoribonucleases
  • tRNase Z, human

Grant support

This work was supported by Adaptable and Seamless Technology Transfer Program through Target-driven R&D, Japan Science and Technology Agency (to MN), the Science Research Promotion Fund from the Promotion and Mutual Aid Corporation for Private Schools of Japan (to MN), and the JSPS KAKENHI Grant Numbers 23650618 (to MN) and 24659269 (to YT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.