Login Register Cart 0
Research Article

Age-Related Argonaute Loading of Ribosomal RNA Fragments

Author(s): Lingyu Guan and Andrey Grigoriev*

Volume 9, Issue 2, 2020

Page: [142 - 152] Pages: 11

DOI: 10.2174/2211536608666190920165705

Open Access Journals Promotions 2
Abstract

Background: Accumulating evidence points to the functional roles of rRNA derived Fragments (rRFs), often considered degradation byproducts. Small RNAs, including miRNAs and tRNA-derived Fragments (tRFs), have been implicated in the aging process and we considered rRFs in this context.

Objective: We performed a computational analysis of Argonaute-loaded rRFs in Drosophila melanogaster to study rRF changes with age. We determined rRF abundance in Ago1 and Ago2 at 3 and 30 days to identify Ago1-guided and Ago2-guided fragments. We searched for putative seed sequences in rRFs based on frequent matches of sliding k-mer windows to the conserved regions of 12 Drosophila genomes. We predicted putative targets (containing matches to seeds identified in four rRFs) and studied their functional enrichments using Gene Ontology.

Results: We identified precise cleavage sites of distinct rRF isoforms from both nuclear and mitochondrial rRNAs. The most prominent rRF isoforms were enriched in Ago2 at 3 days and that loading strongly decreased with age. For less abundant rRFs, loading of Ago2-guided rRFs generally increased in Ago2, whereas Ago1-guided rRFs revealed diverse patterns. The distribution of seed matches in targets suggested that rRFs may bind to various conserved regions of many genes, possibly via miRNA-like seed-based mechanisms.

Conclusion: Our observations suggest that rRFs may be functional molecules, with age-dependent Argonaute loading, comparable to that of miRNAs and tRFs. The putative rRF targets showed significant enrichment in developmental processes and biological regulation, similar to tRFs and consistent with a possible involvement of these newly identified small RNAs in the Drosophila aging.

Keywords: Aging, argonaute, drosophila, ribosomal RNA, rRNA fragments, small RNA.

« Previous Next »
Graphical Abstract

[1]
Maute RL, Schneider C, Sumazin P, et al. tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. Proc Natl Acad Sci USA 2013; 110(4): 1404-9.
[http://dx.doi.org/10.1073/pnas.1206761110] [PMID: 23297232]
[2]
Ivanov P, Emara MM, Villen J, Gygi SP, Anderson P. Angiogenin-induced tRNA fragments inhibit translation initiation. Mol Cell 2011; 43(4): 613-23.
[http://dx.doi.org/10.1016/j.molcel.2011.06.022] [PMID: 21855800]
[3]
Cole C, Sobala A, Lu C, et al. Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs. RNA 2009; 15(12): 2147-60.
[http://dx.doi.org/10.1261/rna.1738409] [PMID: 19850906]
[4]
Li Z, Ender C, Meister G, Moore PS, Chang Y, John B. Extensive terminal and asymmetric processing of small RNAs from rRNAs, snoRNAs, snRNAs, and tRNAs. Nucleic Acids Res 2012; 40(14): 6787-99.
[http://dx.doi.org/10.1093/nar/gks307] [PMID: 22492706]
[5]
Gebetsberger J, Zywicki M, Kunzi A, Polacek N. tRNA-derived fragments target the ribosome and function as regulatory noncoding RNA in Haloferax volcanii. Archaea Int Microbiol J 2012; 11.
[6]
Li Y, Luo J, Zhou H, et al. 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.
[http://dx.doi.org/10.1093/nar/gkn596] [PMID: 18820301]
[7]
Kumar P, Anaya J, Mudunuri SB, Dutta A. Meta-analysis of tRNA derived RNA fragments reveals that they are evolutionarily conserved and associate with AGO proteins to recognize specific RNA targets. BMC Biol 2014; 12: 78.
[http://dx.doi.org/10.1186/s12915-014-0078-0] [PMID: 25270025]
[8]
Luo S, He F, Luo J, et al. Drosophila tsRNAs preferentially suppress general translation machinery via antisense pairing and participate in cellular starvation response. Nucleic Acids Res 2018; 46(10): 5250-68.
[http://dx.doi.org/10.1093/nar/gky189] [PMID: 29548011]
[9]
Lee HC, Chang SS, Choudhary S, et al. qiRNA is a new type of small interfering RNA induced by DNA damage. Nature 2009; 459(7244): 274-7.
[http://dx.doi.org/10.1038/nature08041] [PMID: 19444217 ]
[10]
Chen Z, Sun Y, Yang X, et al. Two featured series of rRNA-derived RNA Fragments (rRFs) constitute a novel class of small RNAs. PLoS One 2017; 12(4) e0176458
[http://dx.doi.org/10.1371/journal.pone.0176458] [PMID: 28441451]
[11]
Wang L, Yu X, Wang H, et al. A novel class of heat-responsive small RNAs derived from the chloroplast genome of Chinese cabbage (Brassica rapa). BMC Genomics 2011; 12: 289.
[http://dx.doi.org/10.1186/1471-2164-12-289] [PMID: 21639890]
[12]
Locati MD, Pagano JFB, Abdullah F, et al. Identifying small RNAs derived from maternal- and somatic-type rRNAs in zebrafish development. Genome 2018; 61(5): 371-8.
[http://dx.doi.org/10.1139/gen-2017-0202] [PMID: 29425468]
[13]
Chen H, Kobayashi K, Miyao A, Hirochika H, Yamaoka N, Nishiguchi M. Both OsRecQ1 and OsRDR1 are required for the production of small RNA in response to DNA-damage in rice. PLoS One 2013; 8(1) e55252
[http://dx.doi.org/10.1371/journal.pone.0055252] [PMID: 23383126]
[14]
Asha S, Soniya EV. The sRNAome mining revealed existence of unique signature small RNAs derived from 5.8SrRNA from Piper nigrum and other plant lineages. Sci Rep 2017; 7: 41052.
[http://dx.doi.org/10.1038/srep41052] [PMID: 28145468]
[15]
Chak LL, Mohammed J, Lai EC, Tucker-Kellogg G, Okamura K. A deeply conserved, noncanonical miRNA hosted by ribosomal DNA. RNA 2015; 21(3): 375-84.
[http://dx.doi.org/10.1261/rna.049098.114] [PMID: 25605965]
[16]
Calabrese JM, Sharp PA. Characterization of the short RNAs bound by the P19 suppressor of RNA silencing in mouse embryonic stem cells. RNA 2006; 12(12): 2092-102.
[http://dx.doi.org/10.1261/rna.224606] [PMID: 17135486]
[17]
García-López J, Hourcade Jde D, Alonso L, Cárdenas DB, del Mazo J. Global characterization and target identification of piRNAs and endo-siRNAs in mouse gametes and zygotes. Biochim Biophys Acta 2014; 1839(6): 463-75.
[http://dx.doi.org/10.1016/j.bbagrm.2014.04.006] [PMID: 24769224]
[18]
Wei H, Zhou B, Zhang F, et al. Profiling and identification of small rDNA-derived RNAs and their potential biological functions. PLoS One 2013; 8(2) e56842
[http://dx.doi.org/10.1371/journal.pone.0056842] [PMID: 23418607]
[19]
Abe M, Naqvi A, Hendriks GJ, et al. Impact of age-associated increase in 2′-O-methylation of miRNAs on aging and neurodegeneration in Drosophila. Genes Dev 2014; 28(1): 44-57.
[http://dx.doi.org/10.1101/gad.226654.113] [PMID: 24395246]
[20]
Kato M, Chen X, Inukai S, Zhao H, Slack FJ. Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans. RNA 2011; 17(10): 1804-20.
[http://dx.doi.org/10.1261/rna.2714411] [PMID: 21810936]
[21]
Karaiskos S, Naqvi AS, Swanson KE, Grigoriev A. Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets. Biol Direct 2015; 10: 51.
[http://dx.doi.org/10.1186/s13062-015-0081-6] [PMID: 26374501]
[22]
Karaiskos S, Grigoriev A. Dynamics of tRNA fragments and their targets in aging mammalian brain. F1000 Res 2016; 5: 5.
[http://dx.doi.org/10.12688/f1000research.10116.1] [PMID: 28105302]
[23]
Thurmond J, Goodman JL, Strelets VB, et al. FlyBase 2.0: the next generation. Nucleic Acids Res 2019; 47(D1): D759-65.
[http://dx.doi.org/10.1093/nar/gky1003] [PMID: 30364959]
[24]
Rosenbloom KR, Armstrong J, Barber GP, et al. The UCSC Genome browser database: 2015 update. Nucleic Acids Res 2015; 43(Database issue): D670-81.
[http://dx.doi.org/10.1093/nar/gku1177] [PMID: 25428374]
[25]
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 2010; 16(1): 43-56.
[http://dx.doi.org/10.1261/rna.1972910] [PMID: 19917635]
[26]
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.
[http://dx.doi.org/10.1101/gad.1837609] [PMID: 19933153]
[27]
Sobala A, Hutvagner G. Transfer RNA-derived fragments: origins, processing, and functions. Wiley Interdiscip Rev RNA 2011; 2(6): 853-62.
[http://dx.doi.org/10.1002/wrna.96] [PMID: 21976287]
[28]
Czech B, Zhou R, Erlich Y, et al. Hierarchical rules for argonaute loading in Drosophila. Mol Cell 2009; 36(3): 445-56.
[http://dx.doi.org/10.1016/j.molcel.2009.09.028] [PMID: 19917252]
[29]
Okamura K, Robine N, Liu Y, Liu Q, Lai EC. R2D2 organizes small regulatory RNA pathways in Drosophila. Mol Cell Biol 2011; 31(4): 884-96.
[http://dx.doi.org/10.1128/MCB.01141-10] [PMID: 21135122]
[30]
Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136(2): 215-33.
[http://dx.doi.org/10.1016/j.cell.2009.01.002] [PMID: 19167326]
[31]
Shin C, Nam JW, Farh KK, Chiang HR, Shkumatava A, Bartel DP. Expanding the microRNA targeting code: functional sites with centered pairing. Mol Cell 2010; 38(6): 789-802.
[http://dx.doi.org/10.1016/j.molcel.2010.06.005] [PMID: 20620952]
[32]
Helwak A, Kudla G, Dudnakova T, Tollervey D. Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell 2013; 153(3): 654-65.
[http://dx.doi.org/10.1016/j.cell.2013.03.043] [PMID: 23622248]
[33]
Kim HK, Fuchs G, Wang S, et al. A transfer-RNA-derived small RNA regulates ribosome biogenesis. Nature 2017; 552(7683): 57-62.
[http://dx.doi.org/10.1038/nature25005] [PMID: 29186115]
[34]
Lee CY, Wilkinson BD, Siegrist SE, Wharton RP, Doe CQ. Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal. Dev Cell 2006; 10(4): 441-9.
[http://dx.doi.org/10.1016/j.devcel.2006.01.017] [PMID: 16549393]
[35]
Sonoda J, Wharton RP. Drosophila brain tumor is a translational repressor. Genes Dev 2001; 15(6): 762-73.
[http://dx.doi.org/10.1101/gad.870801] [PMID: 11274060]
[36]
Blenkiron C, Hurley DG, Fitzgerald S, Print CG, Lasham A. Links between the oncoprotein YB-1 and small non-coding RNAs in breast cancer. PLoS One 2013; 8(11) e80171
[http://dx.doi.org/10.1371/journal.pone.0080171] [PMID: 24260353]

Rights & Permissions Print Cite
Article Metrics
42
8
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy