Stressing Out over tRNA Cleavage

Thompson, Debrah M.; Parker, Roy

doi:10.1016/j.cell.2009.07.001

Cited by 383 publications

(398 citation statements)

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“…Our deep sequencing studies of serum/plasma have consistently detected tRNA‐derived RNAs of size 30–33 nt (Dhahbi et al ., 2013a,b). Intracellular tRNA‐derived small RNAs are classified into two types based on their size (Sobala & Hutvagner, 2011; Martens‐Uzunova et al ., 2013): tRNA halves with size of 30–40 nt produced by cleavage of mature tRNAs, and shorter tRNA‐derived fragments (tRFs) of size 18–22 nt produced from both mature and pre‐tRNAs by Dicer or RNase Z (Thompson et al ., 2008; Cole et al ., 2009; Fu et al ., 2009; Lee et al ., 2009; Thompson & Parker, 2009a; Pederson, 2010; Sobala & Hutvagner, 2011). The tRNA halves class includes 5′‐ and 3′‐tRNA halves that were first observed in stressed cultured cells where they are produced by cleavage of tRNAs near or at the anticodon loop with the ribonuclease Rny1 in Saccharomyces cerevisiae (Thompson & Parker, 2009b) and Angiogenin in higher eukaryotes (Fu et al ., 2009; Yamasaki et al ., 2009).…”

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confidence: 99%

Circulating microRNA signature of genotype‐by‐age interactions in the long‐lived Ames dwarf mouse

et al. 2015

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SummaryRecent evidence demonstrates that serum levels of specific miRNAs significantly change with age. The ability of circulating sncRNAs to act as signaling molecules and regulate a broad spectrum of cellular functions implicates them as key players in the aging process. To discover circulating sncRNAs that impact aging in the long‐lived Ames dwarf mice, we conducted deep sequencing of small RNAs extracted from serum of young and old mice. Our analysis showed genotype‐specific changes in the circulating levels of 21 miRNAs during aging [genotype‐by‐age interaction (GbA)]. Genotype‐by‐age miRNAs showed four distinct expression patterns and significant overtargeting of transcripts involved in age‐related processes. Functional enrichment analysis of putative and validated miRNA targets highlighted cellular processes such as tumor suppression, anti‐inflammatory response, and modulation of Wnt, insulin, mTOR, and MAPK signaling pathways, among others. The comparative analysis of circulating GbA miRNAs in Ames mice with circulating miRNAs modulated by calorie restriction (CR) in another long‐lived mouse suggests CR‐like and CR‐independent mechanisms contributing to longevity in the Ames mouse. In conclusion, we showed for the first time a signature of circulating miRNAs modulated by age in the long‐lived Ames mouse.

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Section: Introductionmentioning

confidence: 99%

Circulating microRNA signature of genotype‐by‐age interactions in the long‐lived Ames dwarf mouse

et al. 2015

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“…Therefore, any change in tRNA availability will impact on protein synthesis rates, especially under stress conditions. The discovery of stress-induced tRNA fragments in many organisms was therefore interpreted as confirmation that tRNA degradation inhibits protein synthesis [4]. Indeed, recent data support the notion that tRNA fragments can selectively inhibit protein synthesis by targeting the translation machinery [5].…”

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“…tRNA-derived fragments are produced by stress-released ribonucleases that cleave mature tRNAs resulting in defined 5 0 -and 3 0 -fragments [4]. While other small non-coding RNAs (i.e.…”

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“…This suggests control mechanisms in order to avoid constant tRNA cleavage and interference with protein synthesis. Indeed, many observations indicated that only a fraction of mature tRNAs is cleaved during the stress response, leaving the total tRNA pool unchanged [4]. This suggests the existence of mechanisms that protect against quantitative tRNA degradation during the stress response and indicates that a major impact of tRNA fragments on protein translation is unlikely.…”

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“…Subcellular sequestration has been observed for Rny1 in yeast (RNase T2 family) and for angiogenin in mammalian cells (RNase A-family) both of which cleave tRNAs under stress conditions. These nucleases are segregated from cytoplasmic RNAs through targeting to membrane-bound organelles (the vacuole in yeast) or by extra-cellular secretion (in the case of angiogenin in mammals) [4]. While stress can release these endonucleases from their ''confinement'', the sub-cellular rearrangement of RNA-containing structures such as processing bodies (P-bodies) and their dynamic interactions with stress-induced structures (e.g.…”

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tRNA modifications: Necessary for correct tRNA‐derived fragments during the recovery from stress?

Durdevic

Schaefer

2013

BioEssays

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Transfer RNA Synthesis and Regulation

Hori

Tomikawa

Hirata

et al. 2014

Encyclopedia of Life Sciences

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Transfer ribonucleic acid (tRNA) , which is primarily transcribed from tRNA genes by RNA polymerase, matures via several steps: processing, splicing, CCA addition and post‐transcriptional modifications. Primary transcripts of tRNA genes contain extra 5′ and 3′ sequences, which are removed by a set of nucleases. In addition, some primary transcripts contain introns, which are spliced out by specific endonucleases or in self‐splicing reactions. The ligation of exons generally requires a tRNA ligase. In some species, the CCA sequences present at the 3′‐termini of all mature tRNAs are not encoded in the tRNA genes, but are added post‐transcriptionally by a CCA‐adding enzyme. All mature tRNA molecules contain modified nucleotides, generated by specific tRNA modification enzymes or guide RNA systems. These modified nucleotides are involved in stabilisation of tRNA structure, decoding, tRNA quality control, regulation of subcellular localisation of tRNAs and immune responses against infectious organisms. Key Concepts: tRNA is transcribed from tRNA genes by RNA polymerase, and matures through processing, splicing, CCA addition and post‐transcriptional modification. Synthesis of tRNA is regulated by promoter activity and specific factors (ppGpp and/or pppGpp in prokaryotes, and Maf1 in eukaryotes), depending on the nutrient conditions of the cell. The relative amounts of tRNA are regulated by several factors: copy number of tRNA genes, transcriptional activity, and degradation by various nucleases. Primary transcripts of tRNA genes contain extra 5′ and 3′ sequences, which are removed by a set of nucleases. In some cases, tRNA transcripts contain introns, which are spliced out by specific endonuclease or the group I intron reaction. The two resultant fragments are joined by RNA ligase or the self‐splicing reaction. CCA‐adding enzyme regulates the amount of active tRNA by introducing the CCA sequence at the C ‐terminus of tRNA. tRNA possesses a variety of modified nucleotides, which are introduced by specific tRNA modification enzymes. Several modifications of tRNA play important roles in the translation process: promotion, expansion, restriction, and/or alteration of codon–anticodon interactions; stabilisation of tRNA structure; recognition by translation factors and aminoacyl‐tRNA synthetases; etc. Several modified nucleotides in tRNA are involved in RNA quality control systems, regulation of tRNA transport, infection and immune responses.

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Stressing Out over tRNA Cleavage

Cited by 383 publications

References 39 publications

Circulating microRNA signature of genotype‐by‐age interactions in the long‐lived Ames dwarf mouse

Circulating microRNA signature of genotype‐by‐age interactions in the long‐lived Ames dwarf mouse

tRNA modifications: Necessary for correct tRNA‐derived fragments during the recovery from stress?

Transfer RNA Synthesis and Regulation

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