Hints of tRNA-Derived Small RNAs Role in RNA Silencing Mechanisms

Abstract

With the advent of new and improved high-throughput sequencing technologies in the last few years, a growing number of novel classes of small RNA, other than miRNAs or siRNA, has emerged, which appear as new actors in gene expression regulation. tRNA-derived small RNAs represent one of these novel members that are, surprisingly, among the most conserved class of small RNAs throughout evolution. They could represent the most primitive small RNA pathways from which the well-known canonical RNA silencing pathways reported in higher eukaryotes evolved. This review aims to make a compilation of the most relevant research literature in this field with the purpose of shedding light on the relation of these primitive tRNA-derived molecules with the gene silencing machinery.

Figure 1

(a) tRNA halves generation from mature tRNAs through the action of anticodon-cleaving enzymes (Angiogenin or Rny1). 5' and 3' halves are depicted in blue and green, respectively. (b) Classification of small tRFs into three groups: 3' U tRFs (yellow), 3' CCA tRFs (light blue) and 5' tRFs (light green). (c) Scheme of the small tRFs biogenesis pathways. 3' U tRFs could be generated in the nucleus by the action of tRNAse Z during the maturation of tRNAs (1) and subsequently exported to the cytoplasm. Alternatively, immature tRNAs could be exported prematurely from the nucleus and be subjected to cleavage by a cytoplasmic pool of tRNAse Z (2). 3' CCA and 5' tRFs can be generated at any point after tRNA processing by tRNAse Z and RNAse P, from either misfolded, properly folded but not aminoacylated or aminoacylated tRNAs (3), through the action of Dicer and possibly other proteins, including Angiogenin.