Abstract
Non-coding small RNAs including tRNA, rRNA, snoRNA, and Y RNA, have been recently shown to undergo processing into smaller RNA molecules (1, 2). These derivatives of known small RNAs are not merely degradation products but are specific cleavage products that function in patho-physiological conditions (3–5). Particularly, tRNAs are processed into two types of tRNA-derived small RNAs (2): (i) The 5′ and 3′ tRNA halves are 30–40 nt long and are produced by cleavage of mature cytoplasmic tRNAs (6). Two ribonucleases have been shown to cleave mature tRNAs near or in the anticodon loop to generate tRNA halves during stress: Rny1 in Saccharomyces cerevisiae (7) and angiogenin in higher eukaryotes (6, 8). (ii) The shorter tRNA-derived fragments (tRFs) are 18–22 nt long, and are produced from both mature and pre-tRNAs by Dicer or RNase Z. Here, I will consider only the tRNA halves and argue their potential as immune signaling molecules.
Highlights
Initial reports showed that tRNA halves accumulate in Tetrahymena thermophila [9] and Trypanosoma cruzi [10] subjected to nutritional stress, and in S. cerevisiae, plants, and human cell lines where they become highly induced during oxidative stress conditions [8, 11]
We have found that mouse spleen, lymph nodes, and fetal liver, which is a hematopoietic tissue, leukocytes, bone marrow, and thymus, and human leukocytes contain considerable amounts of 5 tRNA halves when compared to mouse non-hematopoietic tissues, which showed only traces of 5 tRNA halves [Figure 1; [22]]
Using deep sequencing of serum small RNAs, we and others detected 5 tRNA halves circulating in mouse and human bloodstream [31, 32], they were later found in rat and monkey serum at levels higher than miRNAs [23]
Summary
Initial reports showed that tRNA halves accumulate in Tetrahymena thermophila [9] and Trypanosoma cruzi [10] subjected to nutritional stress, and in S. cerevisiae, plants, and human cell lines where they become highly induced during oxidative stress conditions [8, 11]. Many studies indicate that some organisms and cell types express tRNA halves constitutively, while others produce them under stress conditions. The very small amounts of 5 tRNA halves we detected in nonhematopoietic tissues are comparable to the levels observed by Fu and colleagues in normal fresh mouse liver and heart tissues [see Figure 2 in Ref.
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