Biology Direct | |
Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets | |
Spyros Karaiskos1  Ammar S. Naqvi1  Karl E. Swanson1  Andrey Grigoriev1  | |
[1] Department of BiologyCenter for Computational and Integrative Biology, Rutgers University, Camden 08102, NJ, USA | |
关键词: tRF; tRNA; ncRNA; Small RNA; Aging; Argonaute; RISC; | |
Others : 1230705 DOI : 10.1186/s13062-015-0081-6 |
|
received in 2015-03-13, accepted in 2015-09-07, 发布年份 2015 | |
【 摘 要 】
Background
Development of sequencing technologies and supporting computation enable discovery of small RNA molecules that previously escaped detection or were ignored due to low count numbers. While the focus in the analysis of small RNA libraries has been primarily on microRNAs (miRNAs), recent studies have reported findings of fragments of transfer RNAs (tRFs) across a range of organisms.
Results
Here we describe Drosophila melanogaster tRFs, which appear to have a number of structural and functional features similar to those of miRNAs but are less abundant. As is the case with miRNAs, (i) tRFs seem to have distinct isoforms preferentially originating from 5’ or 3’ end of a precursor molecule (in this case, tRNA), (ii) ends of tRFs appear to contain short “seed” sequences matching conserved regions across 12 Drosophila genomes, preferentially in 3’ UTRs but also in introns and exons; (iii) tRFs display specific isoform loading into Ago1 and Ago2 and thus likely function in RISC complexes; (iii) levels of loading in Ago1 and Ago2 differ considerably; and (iv) both tRF expression and loading appear to be age-dependent, indicating potential regulatory changes from young to adult organisms.
Conclusions
We found that Drosophila tRF reads mapped to both nuclear and mitochondrial tRNA genes for all 20 amino acids, while previous studies have usually reported fragments from only a few tRNAs. These tRFs show a number of similarities with miRNAs, including seed sequences. Based on complementarity with conserved Drosophila regions we identified such seed sequences and their possible targets with matches in the 3’UTR regions. Strikingly, the potential target genes of the most abundant tRFs show significant Gene Ontology enrichment in development and neuronal function. The latter suggests that involvement of tRFs in the RNA interfering pathway may play a role in brain activity or brain changes with age.
Reviewers
This article was reviewed by Eugene Koonin, Neil Smalheiser and Alexander Kel.
【 授权许可】
2015 Karaiskos et al.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20151107033022855.pdf | 2238KB | download | |
Fig. 6. | 42KB | Image | download |
Fig. 5. | 28KB | Image | download |
Fig. 4. | 46KB | Image | download |
Fig. 3. | 29KB | Image | download |
Fig. 2. | 34KB | Image | download |
Fig. 1. | 48KB | Image | download |
【 图 表 】
Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
【 参考文献 】
- [1]Gong B, Lee YS, Lee I, Shelite TR, Kunkeaw N, Xu G, Lee K, Jeon SH, Johnson BH, Chang Q, et al.: Compartmentalized, functional role of angiogenin during spotted fever group rickettsia-induced endothelial barrier dysfunction: evidence of possible mediation by host tRNA-derived small noncoding RNAs. BMC Infect Dis 2013, 13:285. BioMed Central Full Text
- [2]Li Y, Luo J, Zhou H, Liao JY, Ma LM, Chen YQ, Qu LH: Stress-induced tRNA-derived RNAs: a novel class of small RNAs in the primitive eukaryote Giardia lamblia. Nucleic Acids Res 2008, 36(19):6048-55.
- [3]Wei C, Salichos L, Wittgrove CM, Rokas A, Patton JG: Transcriptome-wide analysis of small RNA expression in early zebrafish development. RNA 2012, 18(5):915-29.
- [4]Thompson DM, Parker R: The RNase Rny1p cleaves tRNAs and promotes cell death during oxidative stress in Saccharomyces cerevisiae. J Cell Biol 2009, 185(1):43-50.
- [5]Tuck AC, Tollervey D: RNA in pieces. Trends Genet 2011, 27(10):422-32.
- [6]Lee YS, Shibata Y, Malhotra A, Dutta A: A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev 2009, 23(22):2639-49.
- [7]Sobala A, Hutvagner G: Transfer RNA-derived fragments: origins, processing, and functions. Wiley Interdiscip Rev RNA 2007, 2(6):853-62.
- [8]Anderson P, Ivanov P. tRNA fragments in human health and disease. FEBS Lett. 2014;4297–4304.
- [9]Gebetsberger J, Zywicki M, Kunzi A, Polacek N: tRNA-derived fragments target the ribosome and function as regulatory non-coding RNA in Haloferax volcanii. Archaea 2012, 2012:260909.
- [10]Miyoshi K, Miyoshi T, Siomi H: Many ways to generate microRNA-like small RNAs: non-canonical pathways for microRNA production. Mol Genet Genomics 2010, 284(2):95-103.
- [11]Loss-Morais G, Waterhouse PM, Margis R: Description of plant tRNA-derived RNA fragments (tRFs) associated with argonaute and identification of their putative targets. Biol Direct 2014, 8:6. BioMed Central Full Text
- [12]Fischer S, Benz J, Spath B, Jellen-Ritter A, Heyer R, Dorr M, Maier LK, Menzel-Hobeck C, Lehr M, Jantzer K, et al.: Regulatory RNAs in Haloferax volcanii. Biochem Soc Trans 2011, 39(1):159-62.
- [13]Garcia-Silva MR, Cabrera-Cabrera F, Guida MC, Cayota A: Hints of tRNA-derived small RNAs role in RNA silencing mechanisms. Genes (Basel) 2012, 3(4):603-14.
- [14]Ivanov P, Emara MM, Villen J, Gygi SP, Anderson P: Angiogenin-induced tRNA fragments inhibit translation initiation. Mol Cell 2011, 43(4):613-23.
- [15]Wang Q, Lee I, Ren J, Ajay SS, Lee YS, Bao X: Identification and functional characterization of tRNA-derived RNA fragments (tRFs) in respiratory syncytial virus infection. Mol Ther 2012, 21(2):368-79.
- [16]Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP: MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 2007, 27(1):91-105.
- [17]Lewis BP, Burge CB, Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005, 120(1):15-20.
- [18]Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB: Prediction of mammalian microRNA targets. Cell 2003, 115(7):787-98.
- [19]Haiser HJ, Karginov FV, Hannon GJ, Elliot MA: Developmentally regulated cleavage of tRNAs in the bacterium Streptomyces coelicolor. Nucleic Acids Res 2008, 36(3):732-41.
- [20]Maute RL, Schneider C, Sumazin P, Holmes A, Califano A, Basso K, Dalla-Favera R: tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. Proc Natl Acad Sci U S A 2013, 110(4):1404-9.
- [21]Abe M, Naqvi A, Hendriks GJ, Feltzin V, Zhu Y, Grigoriev A, Bonini NM: Impact of age-associated increase in 2’-O-methylation of miRNAs on aging and neurodegeneration in Drosophila. Genes Dev 2014, 28(1):44-57.
- [22]Liu N, Abe M, Sabin LR, Hendriks GJ, Naqvi AS, Yu Z, Cherry S, Bonini NM: The exoribonuclease Nibbler controls 3’ end processing of microRNAs in Drosophila. Curr Biol 2011, 21(22):1888-93.
- [23]Peng H, Shi J, Zhang Y, Zhang H, Liao S, Li W, Lei L, Han C, Ning L, Cao Y, et al.: A novel class of tRNA-derived small RNAs extremely enriched in mature mouse sperm. Cell Res 2012, 22(11):1609-12.
- [24]Naqvi A, Cui T, Grigoriev A: Visualization of nucleotide substitutions in the (micro) transcriptome. BMC Genomics 2014, 15(Suppl 4):S9. BioMed Central Full Text
- [25]Chen CJ, Liu Q, Zhang YC, Qu LH, Chen YQ, Gautheret D: Genome-wide discovery and analysis of microRNAs and other small RNAs from rice embryogenic callus. RNA Biol 2011, 8(3):538-47.
- [26]Ghildiyal M, Xu J, Seitz H, Weng Z, Zamore PD: Sorting of Drosophila small silencing RNAs partitions microRNA* strands into the RNA interference pathway. RNA 2009, 16(1):43-56.
- [27]Kim VN: MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 2005, 6(5):376-85.
- [28]Jochl C, Rederstorff M, Hertel J, Stadler PF, Hofacker IL, Schrettl M, Haas H, Huttenhofer A: Small ncRNA transcriptome analysis from Aspergillus fumigatus suggests a novel mechanism for regulation of protein synthesis. Nucleic Acids Res 2008, 36(8):2677-89.
- [29]Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell 2009, 136(2):215-33.
- [30]Shin C, Nam J-W, Farh KK-H, Chiang HR, Shkumatava A, Bartel DP: Expanding the microRNA targeting code: functional sites with centered pairing. Mol Cell 2010, 38(6):789-802.
- [31]Clark AG, Eisen MB, Smith DR, Bergman CM, Oliver B, Markow TA, Kaufman TC, Kellis M, Gelbart W, Iyer VN, et al.: Evolution of genes and genomes on the Drosophila phylogeny. Nature 2007, 450(7167):203-18.
- [32]Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al.: Gene ontology: tool for the unification of biology. The gene ontology consortium. Nat Genet 2000, 25(1):25-9.
- [33]Prakash S, McLendon HM, Dubreuil CI, Ghose A, Hwa J, Dennehy KA, Tomalty KM, Clark KL, Van Vactor D, Clandinin TR: Complex interactions amongst N-cadherin, DLAR, and Liprin-alpha regulate Drosophila photoreceptor axon targeting. Dev Biol 2009, 336(1):10-9.
- [34]Krueger NX, Van Vactor D, Wan HI, Gelbart WM, Goodman CS, Saito H: The transmembrane tyrosine phosphatase DLAR controls motor axon guidance in Drosophila. Cell 1996, 84(4):611-22.
- [35]Smibert P, Miura P, Westholm JO, Shenker S, May G, Duff MO, Zhang D, Eads BD, Carlson J, Brown JB: Global patterns of tissue-specific alternative polyadenylation in Drosophila. Cell reports 2012, 1(3):277-89.
- [36]Iwasaki S, Kawamata T, Tomari Y: Drosophila argonaute1 and argonaute2 employ distinct mechanisms for translational repression. Mol Cell 2009, 34(1):58-67.
- [37]Bai H, Kang P, Hernandez AM, Tatar M: Activin signaling targeted by insulin/dFOXO regulates aging and muscle proteostasis in Drosophila. PLoS Genet 2013, 9(11):e1003941.
- [38]Goodarzi H, Liu X, Nguyen Hoang CB, Zhang S, Fish L, Tavazoie Sohail F: Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement. Cell 2015, 161(4):790-802.
- [39]Taliaferro JM, Aspden JL, Bradley T, Marwha D, Blanchette M, Rio DC: Two new and distinct roles for Drosophila Argonaute-2 in the nucleus: alternative pre-mRNA splicing and transcriptional repression. Genes Dev 2013, 27(4):378-89.
- [40]Moreau MP, Bruse SE, David-Rus R, Buyske S, Brzustowicz LM: Altered microRNA expression profiles in postmortem brain samples from individuals with schizophrenia and bipolar disorder. Biol Psychiatry 2011, 69(2):188-93.
- [41]Perkins DO, Jeffries CD, Jarskog LF, Thomson JM, Woods K, Newman MA, Parker JS, Jin J, Hammond SM: microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol 2007, 8(2):R27. BioMed Central Full Text
- [42]Tan H, Poidevin M, Li H, Chen D, Jin P: MicroRNA-277 modulates the neurodegeneration caused by Fragile X premutation rCGG repeats. PLoS Genet 2012., 8(5) Article ID e1002681
- [43]Zhang Y, Guo H, Kwan H, Wang JW, Kosek J, Lu B: PAR-1 kinase phosphorylates Dlg and regulates its postsynaptic targeting at the Drosophila neuromuscular junction. Neuron 2007, 53(2):201-15.
- [44]Kumar V, Fricke R, Bhar D, Reddy-Alla S, Krishnan KS, Bogdan S, Ramaswami M: Syndapin promotes formation of a postsynaptic membrane system in Drosophila. Mol Biol Cell 2009, 20(8):2254-64.
- [45]Azim AC, Knoll JH, Marfatia SM, Peel DJ, Bryant PJ, Chishti AH: DLG1: chromosome location of the closest human homologue of the Drosophila discs large tumor suppressor gene. Genomics 1995, 30(3):613-6.
- [46]McIlroy G, Foldi I, Aurikko J, Wentzell JS, Lim MA, Fenton JC, Gay NJ, Hidalgo A: Toll-6 and Toll-7 function as neurotrophin receptors in the Drosophila melanogaster CNS. Nat Neurosci 2013, 16(9):1248-56.
- [47]Garber K, Smith KT, Reines D, Warren ST: Transcription, translation and fragile X syndrome. Curr Opin Genet Dev 2006, 16(3):270-5.
- [48]Jin P, Zarnescu DC, Ceman S, Nakamoto M, Mowrey J, Jongens TA, Nelson DL, Moses K, Warren ST: Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nat Neurosci 2004, 7(2):113-7.
- [49]Ishizuka A, Siomi MC, Siomi H: A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes Dev 2002, 16(19):2497-508.
- [50]Rosenbloom KR, Armstrong J, Barber GP, Casper J, Clawson H, Diekhans M, et al. The UCSC genome browser database: 2015 update. Nucleic Acids Res. 2014.