The RNA Methyltransferase Dnmt2 Is Required for Efficient Dicer-2-Dependent siRNA Pathway Activity in Drosophila

Durdevic, Zeljko; Mobin, Mehrpouya Balaghy; Hanna, Katharina; Lyko, Frank; Schaefer, Matthias

doi:10.1016/j.celrep.2013.07.046

Cited by 112 publications

(112 citation statements)

References 27 publications

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…It was shown that tRNA halves may not only regulate translation, but also small RNA homeostasis during heat-shock. 53 Increased tRNA cleavage, induced by decreased tRNA stability (e.g., under certain stress conditions or lacking methylation in the anticodon loop), seems to interfere with the small-interfering RNA (siRNA) pathway through binding of tRNA halves to Dicer-2 ( Fig. 1).…”

Section: Trna In Piecesmentioning

confidence: 99%

Slicing tRNAs to boost functional ncRNA diversity

2013

View full text Add to dashboard Cite

Section: Trna In Piecesmentioning

confidence: 99%

Slicing tRNAs to boost functional ncRNA diversity

2013

View full text Add to dashboard Cite

“…Increased tRNA cleavage during heat shock in flies lacking the Dnmt2 modification enzyme has been shown to interfere with the siRNA pathway. tiRNAs bind to Dicer and saturate its binding pocket, thus reducing its ability to cleave dsRNAs (31). In an alternative mechanism, tRFs serve as substrates for the cellular RNAi machinery.…”

Section: Role Of Tirnas In the Cellular Stress Response And Other Patmentioning

confidence: 99%

The Many Virtues of tRNA-derived Stress-induced RNAs (tiRNAs): Discovering Novel Mechanisms of Stress Response and Effect on Human Health

Saikia

Hatzoglou

2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

In mammalian cells, mature tRNAs are cleaved by stress-activated ribonuclease angiogenin to generate 5-and 3-tRNA halves: a novel class of small non-coding RNAs of 30 -40 nucleotides in length. The biogenesis and biological functions of tRNA halves are emerging areas of research. This review will discuss the most recent findings on: (i) the mechanism and regulation of their biogenesis, (ii) their mechanism of action (we will specifically discuss their role in the protein synthesis inhibition and the intrinsic pathway of apoptosis), and (iii) their effects on the human physiology and disease conditions. Recent breakthroughs in high-throughput sequencing have led to a more comprehensive view of the cellular transcriptome. We are now aware of numerous additional non-protein-coding RNA (ncRNA) 3 candidates in all three domains of life, thus indicating a hidden layer of transcriptome complexity (1, 2). A more recent development in our understanding of the complexity of cellular RNomes arose with the exciting discovery that ncRNA transcripts with well described functions, such as the tRNAs, can serve as precursors for downstream cleavage events, generating yet another class of functional RNA fragments. Two major classes of tRNA fragments have been identified in human cells. The 17-26-nucleotide long tRNA-derived RNA fragments (tRFs) are products of precise processing at the 5Ј-or 3Ј-end of mature or precursor tRNAs. The tRF-5 and tRF-3 are derived from terminal ends of mature tRNAs, whereas tRF-1 are 3Ј-trailer sequences of pre-tRNAs (3). The other important class of tRNA fragments found in mammalian cells and tissues is the tRNA-derived stress-induced RNAs (tiRNAs). tiRNAs were first reported in human fetus hepatic tissue (4) and human osteosarcoma cells (U2OS), respectively (5). tRFs and tiRNAs are the newest members of the cellular ncRNA repertoire that are found in several organisms and play prominent roles in various cellular functions (6). These tRNA fragments can be generated in cells under physiological conditions and also produced as part of the cellular stress response (4 -9). In mammalian cells, tiRNAs are produced by the cleavage of mature tRNAs at positions close to the anticodon, giving rise to the 30 -40-nucleotide-long 5Ј-and 3Ј-tRNA halves, a term used interchangeably with 5Ј-and 3Ј-tiRNAs throughout this review. The enzyme responsible for this endonucleolytic cleavage is angiogenin (ANG) (4,5). ANG is a member of the pancreatic RNase superfamily distinguished by its potent in vivo angiogenic activity as well as its prominent role in cancer development and neurodegeneration (10, 11). Here we will review the ANG-induced tRNA halves (tiRNAs), their role in mammalian stress response mechanisms, and other cellular functions. Additionally, we will discuss their potential implications in the pathobiology of human diseases with a special focus on neurodegenerative disorders. ANG-induced tRNA Cleavage in Mammalian CellsEndonucleolytic cleavage of mammalian tRNAs by ANG was reported by two research groups in...

show abstract

“…53 Similarly, TRDMT1 mutant flies contain stress induced tRNA fragments and constitutively upregulate the innate immune system. 57,58 …”

Section: 38mentioning

confidence: 99%