piRNAQuest: searching the piRNAome for silencers

BMC Genomics

Zhumur Ghosh¹  Sudipto Saha¹  Ranjan Kumar Maji¹  Arijita Sarkar¹ 

[1] Bioinformatics Centre, Bose Institute, Kolkata 700054, India

关键词: Spermatogenesis;    Stem cells;    Motif;    Transposable element;    Cluster;    Repeat element;    piRNA;   

Others  :  1216540
DOI  :  10.1186/1471-2164-15-555

 received in 2014-02-10, accepted in 2014-06-26,  发布年份 2014

【 摘 要 】

Background

PIWI-interacting RNA (piRNA) is a novel and emerging class of small non-coding RNA (sncRNA). Ranging in length from 26-32 nucleotides, this sncRNA is a potent player in guiding the vital regulatory processes within a cellular system. Inspite of having such a wide role within cellular systems, piRNAs are not well organized and classified, so that a researcher can pool out the biologically relevant information concerning this class.

Description

Here we present piRNAQuest- a unified and comprehensive database of 41749 human, 890078 mouse and 66758 rat piRNAs obtained from NCBI and different small RNA sequence experiments. This database provides piRNA annotation based on their localization in gene, intron, intergenic, CDS, 5^/UTR, 3^/UTR and repetitive regions which has not been done so far. We have also annotated piRNA clusters and have elucidated characteristic motifs within them. We have looked for the presence of piRNAs and piRNA clusters in pseudogenes, which are known to regulate the expression of protein coding transcripts by generating small RNAs. All these will help researchers progress towards solving the unanswered queries on piRNA biogenesis and their mode of action. Further, expression profile for piRNA in different tissues and from different developmental stages has been provided. In addition, we have provided several tools like 'homology search’, 'dynamic cluster search’ and 'pattern search’. Overall, piRNAQuest will serve as a useful resource for exploring human, mouse and rat piRNAome. The database is freely accessible and available at http://bicresources.jcbose.ac.in/zhumur/pirnaquest/ webcite.

Conclusion

piRNAs play a remarkable role in stem cell self-renewal and various vital processes of developmental biology. Although researchers are mining different features on piRNAs, the exact regulatory mechanism is still fuzzy. Thus, understanding the true potential of these small regulatory molecules with respect to their origin, localization and mode of biogenesis is crucial. piRNAQuest will provide us with a better insight on piRNA origin and function which will help to explore the true potential of these sncRNAs.

【 授权许可】

   
2014 Sarkar et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Eddy SR: Non-coding RNA genes and the modern RNA world. Nat Rev Genet 2001, 2(12):919-929.
• [2]Sana J, Faltejskova P, Svoboda M, Slaby O: Novel classes of non-coding RNAs and cancer. J Transl Med 2012, 10:103.
• [3]Aravin A, Gaidatzis D, Pfeffer S, Lagos-Quintana M, Landgraf P, Iovino N, Morris P, Brownstein MJ, Kuramochi-Miyagawa S, Nakano T, Chien M, Russo JJ, Ju J, Sheridan R, Sander C, Zavolan M, Tuschl T: A novel class of small RNAs bind to MILI protein in mouse testes. Nature 2006, 442(7099):203-207.
• [4]Lau NC, Seto AG, Kim J, Kuramochi-Miyagawa S, Nakano T, Bartel DP, Kingston RE: Characterization of the piRNA complex from rat testes. Science 2006, 313(5785):363-367.
• [5]Girard A, Sachidanandam R, Hannon GJ, Carmell MA: A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 2006, 442(7099):199-202.
• [6]Grivna ST, Beyret E, Wang Z, Lin H: A novel class of small RNAs in mouse spermatogenic cells. Genes Dev 2006, 20(13):1709-1714.
• [7]Grivna ST, Pyhtila B, Lin H: MIWI associates with translational machinery and PIWI-interacting RNAs (piRNAs) in regulating spermatogenesis. Proc Natl Acad Sci U S A 2006, 103(36):13415-13420.
• [8]Kim VN: Small RNAs just got bigger: Piwi-interacting RNAs (piRNAs) in mammalian testes. Genes Dev 2006, 20(15):1993-1997.
• [9]Aravin AA, Hannon GJ, Brennecke J: The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race. Science 2007, 318(5851):761-764.
• [10]Heyn H, Ferreira HJ, Bassas L, Bonache S, Sayols S, Sandoval J, Esteller M, Larriba S: Epigenetic disruption of the PIWI pathway in human spermatogenic disorders. PLoS One 2012, 7(10):e47892.
• [11]Zheng K, Wang PJ: Blockade of pachytenepiRNA biogenesis reveals a novel requirement for maintaining post-meiotic germline genome integrity. PLoS Genet 2012, 8(11):e1003038.
• [12]Liu X, Sun Y, Guo J, Ma H, Li J, Dong B, Jin G, Zhang J, Wu J, Meng L, Shou C: Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells. Int J Cancer 2006, 118(8):1922-1929.
• [13]Qiao D, Zeeman AM, Deng W, Looijenga LH, Lin H: Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene 2002, 21(25):3988-3999.
• [14]Thomson T, Lin H: The biogenesis and function of PIWI proteins and piRNAs: progress and prospect. Annu Rev Cell Dev Biol 2009, 25:355-376.
• [15]Gan H, Lin X, Zhang Z, Zhang W, Liao S, Wang L, Han C: piRNA profiling during specific stages of mouse spermatogenesis. RNA 2011, 17(7):1191-1203.
• [16]Brennecke J, Aravin AA, Stark A, Dus M, Kellis M, Sachidanandam R, Hannon GJ: Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell 2007, 128(6):1089-1103.
• [17]Beyret E, Liu N, Lin H: piRNA biogenesis during adult spermatogenesis in mice is independent of the ping-pong mechanism. Cell Res 2012, 22(10):1429-1439.
• [18]Pink RC, Wicks K, Caley DP, Punch EK, Jacobs L, Carter DR: Pseudogenes: pseudo-functional or key regulators in health and disease? RNA 2011, 17(5):792-798.
• [19]Hartig JV, Tomari Y, Forstemann K: piRNAs–the ancient hunters of genome invaders. Genes Dev 2007, 21(14):1707-1713.
• [20]Nordstrand LM, Furu K, Paulsen J, Rognes T, Klungland A: Alkbh1 and Tzfp repress a non-repeat piRNA cluster in pachytene spermatocytes. Nucleic Acids Res 2012, 40(21):10950-10963.
• [21]Sai Lakshmi S, Agrawal S: piRNABank: a web resource on classified and clustered Piwi-interacting RNAs. Nucleic Acids Res 2008, 36(Database issue):D173-D177.
• [22]Liu C, Bai B, Skogerbo G, Cai L, Deng W, Zhang Y, Bu D, Zhao Y, Chen R: NONCODE: an integrated knowledge database of non-coding RNAs. Nucleic Acids Res 2005, 33(Database issue):D112-D115.
• [23]Pang KC, Stephen S, Engstrom PG, Tajul-Arifin K, Chen W, Wahlestedt C, Lenhard B, Hayashizaki Y, Mattick JS: RNAdb–a comprehensive mammalian noncoding RNA database. Nucleic Acids Res 2005, 33(Database issue):D125-D130.
• [24]Rosenkranz D, Zischler H: proTRAC–a software for probabilistic piRNA cluster detection, visualization and analysis. BMC Bioinformatics 2012, 13:5.
• [25]Yang JH, Shao P, Zhou H, Chen YQ, Qu LH: deepBase: a database for deeply annotating and mining deep sequencing data. Nucleic Acids Res 2010, 38(Database issue):D123-D130.
• [26]Rebhan M, Chalifa-Caspi V, Prilusky J, Lancet D: GeneCards: integrating information about genes, proteins and diseases. Trends Genet 1997, 13(4):163.
• [27]Jenuth JP: The NCBI. Publicly available tools and resources on the Web. Methods Mol Biol 2000, 132:301-312.
• [28]Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Wheeler DL: GenBank. Nucleic Acids Res 2006, 34(Database issue):D16-D20.
• [29]Edgar R, Domrachev M, Lash AE: Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 2002, 30(1):207-210.
• [30]Zhang Y, Wang X, Kang L: A k-mer scheme to predict piRNAs and characterize locust piRNAs. Bioinformatics 2011, 27(6):771-776.
• [31]Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ: Basic local alignment search tool. J Mol Biol 1990, 215(3):403-410.
• [32]Karolchik D, Baertsch R, Diekhans M, Furey TS, Hinrichs A, Lu YT, Roskin KM, Schwartz M, Sugnet CW, Thomas DJ, Weber RJ, Haussler D, Kent WJ: The UCSC genome browser database. Nucleic Acids Res 2003, 31(1):51-54.
• [33]Jung I, Park JC, Kim S: piClust: a density based piRNA clustering algorithm. Comput Biol Chem 2014, 50:60-67.
• [34]Sun H, Palaniswamy SK, Pohar TT, Jin VX, Huang THM, Davuluri RV: MPromDb: an integrated resource for annotation and visualization of mammalian gene promoters and ChIP-chip experimental data. Nucleic Acids Res 2006, 34:D98-D103.
• [35]Li XZ, Roy CK, Dong X, Bolcun-Filas E, Wang J, Han BW, Xu J, Moore MJ, Schimenti JC, Weng Z, Zamore PD: An ancient transcription factor initiates the burst of piRNA production during early meiosis in mouse testes. Mol Cell 2013, 50(1):67-81.
• [36]Kim M, Patel B, Schroeder KE, Raza A, Dejong J: Organization and transcriptional output of a novel mRNA-like piRNA gene (mpiR) located on mouse chromosome 10. RNA 2008, 14(6):1005-1011.
• [37]Skinner ME, Uzilov AV, Stein LD, Mungall CJ, Holmes IH: JBrowse: a next-generation genome browser. Genome Res 2009, 19(9):1630-1638.
• [38]Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, Rinn JL: Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev 2011, 25(18):1915-1927.
• [39]Griffiths-Jones S, Grocock RJ, Van Dongen S, Bateman A, Enright AJ: miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 2006, 34(Database issue):D140-D144.
• [40]Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, Ren JY, Li WW, Noble WS: MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res 2009, 37:W202-W208.
• [41]Revanna KV, Chiu CC, Bierschank E, Dong Q: GSV: a web-based genome synteny viewer for customized data. BMC Bioinformatics 2011, 12:316.
• [42]Karro JE, Yan Y, Zheng D, Zhang Z, Carriero N, Cayting P, Harrrison P, Gerstein M: Pseudogene.org: a comprehensive database and comparison platform for pseudogene annotation. Nucleic Acids Res 2007, 35(Database issue):D55-D60.
• [43]Bailey TL, Gribskov M: Combining evidence using p-values: application to sequence homology searches. Bioinformatics 1998, 14(1):48-54.
• [44]Grant CE, Bailey TL, Noble WS: FIMO: scanning for occurrences of a given motif. Bioinformatics 2011, 27(7):1017-1018.
• [45]Buske FA, Boden M, Bauer DC, Bailey TL: Assigning roles to DNA regulatory motifs using comparative genomics. Bioinformatics 2010, 26(7):860-866.
• [46]Robine N, Lau NC, Balla S, Jin Z, Okamura K, Kuramochi-Miyagawa S, Blower MD, Lai EC: A broadly conserved pathway generates 3′UTR-directed primary piRNAs. Curr Biol 2009, 19(24):2066-2076.
• [47]Duret L, Chureau C, Samain S, Weissenbach J, Avner P: The Xist RNA gene evolved in eutherians by pseudogenization of a protein-coding gene. Science 2006, 312(5780):1653-1655.
• [48]Tam OH, Aravin AA, Stein P, Girard A, Murchison EP, Cheloufi S, Hodges E, Anger M, Sachidanandam R, Schultz RM, Hannon GJ: Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 2008, 453(7194):534-538.
• [49]Watanabe T, Totoki Y, Toyoda A, Kaneda M, Kuramochi-Miyagawa S, Obata Y, Chiba H, Kohara Y, Kono T, Nakano T, Surani MA, Sakaki Y, Sasaki H: Endogenous siRNAsfrom naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 2008, 453(7194):539-543.
• [50]Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP: A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 2010, 465(7301):1033-1038.