Transfer RNA as a Source of Small Functional RNA

Review Article

J Mol Biol & Mol Imaging. 2014;1(2): 8.

Transfer RNA as a Source of Small Functional RNA

Megumi Shigematsu, Shozo Honda and Yohei Kirino*

Computational Medicine Center, Department of Biochemistry and Molecular Biology, Sidney Kimmel Medical College, Thomas Jefferson University, USA

*Corresponding author: Yohei Kirino, Computational Medicine Center, Department of Biochemistry and Molecular Biology, Sidney Kimmel Medical College, Thomas Jefferson University, USA

Received: September 09, 2014; Accepted: October 04, 2014; Published: October 08, 2014


Since their discovery in the 1950s, transfer RNAs ( tRNAs ) have been best known as adapter molecules that play a central role in translating genetic information. However, recent biochemical and bioinformatics evidence has led to a previously unexpected conceptual consensus that tRNAs are not always end products; they further serve as a source of small functional RNAs. In many organisms, specific tRNA fragments are produced from mature tRNAs or their precursor transcripts not as random degradation products, but as functional molecules involved in many biological processes beyond translation. In this review, we summarize recent studies of tRNA fragments that have provided new insights into tRNA biology by examining the molecular functions of tRNA fragments and proteins with which they interact.

Keywords: tRNA; tRNA fragment; tRNA half; tRF; Argonaute


The groundbreaking development of next-generation sequencing (NGS) technologies has dramatically advanced our understanding of the cellular transcriptome, revealing that non-protein-coding regions of the genome are widely transcribed, and the generated non-coding RNAs (ncRNAs) play important roles in normal biological processes and diseases [1]. Within the diverse group of ncRNAs, the functional significance is particularly evident for small regulatory RNAs which direct the highly-specific regulation of gene expression by recognizing their complementary RNA targets [2-4]. To date, the following three major classes of small regulatory RNAs have been reported: micro RNAs (miRNAs), short-interfering RNAs (siRNAs), and PIWIinteracting RNAs (piRNAs). The definitive features of these RNAs are their short lengths of 20-31 nucleotides (nt) and their interaction with Argonaute family proteins to form effectors ribonucleoprotein complexes. miRNAs, the best-studied class of small regulatory RNAs, repress complementary target mRNA expression, which is estimated to regulate the expression of most protein-coding genes [5, 6]. Thus, small regulatory RNAs constitute one of the most abundant gene expression regulators and exhibit a tremendous impact on all biological processes by shaping the transcriptome. Although such small RNAs have been the focus of much attention over the recent years, NGS studies combined with RNA biochemical studies have revealed the existence of many different other functional small ncRNAs in the cellular transcriptom'e, including small RNA fragments from transfer RNAs (tRNAs), which we will highlight in this review.

Unexpected Expansion of the tRNA World

tRNAs are universally expressed in all three domains of life, and play a central role in gene expression as adapter molecules 'that translate codons in mRNA into amino acids in protein. Since their discovery in the 1950s, extensive studies have clearly defined their biological properties [7]. tRNAs are 70-90 nt in length and form as cloverleaf secondary structure containing three major loops (D-, T-, and anticodon loops) and four stems (acceptor-, D-, T-, and anticodon stems) (Figure 1). These loops and stems fold into an L-shaped tertiary structure. Over 500 tRNA genes are encoded in the human genome [8], and tRNAs have long half-lives, estimated on the order of days in tissues[9, 10]. Active transcription from multiple sites and high stability place tRNAs among the most abundant RNA molecules, occupying around 15% of the cellular RNA transcriptome.

Citation: Shigematsu M, Honda S and Kirino Y. Transfer RNA as a Source of Small Functional RNA. J Mol Biol& Mol Imaging. 2014;1(2): 8. ISSN:2471-0237