piRNA-like small RNAs mark extended 3’UTRs present in germ and somatic cells

BMC Genomics

Dario Boffelli¹  David IK Martin¹  Joseph Dhahbi¹  Seok-Jin Heo¹  Jennifer Yamtich¹ 

[1] Children’s Hospital Oakland Research Institute, Oakland 94609, CA, USA

关键词: MIWI2;    Somatic;    3’ UTR;    piRNA;   

Others  :  1216172
DOI  :  10.1186/s12864-015-1662-6

 received in 2014-12-23, accepted in 2015-05-29,  发布年份 2015

【 摘 要 】

Background

Piwi-interacting RNAs (piRNAs) are a class of small RNAs; distinct types of piRNAs are expressed in the mammalian testis at different stages of development. The function of piRNAs expressed in the adult testis is not well established. We conducted a detailed characterization of piRNAs aligning at or near the 3’ UTRs of protein-coding genes in a deep dataset of small RNAs from adult mouse testis.

Results

We identified 2710 piRNA clusters associated with 3’ UTRs, including 1600 that overlapped genes not previously associated with piRNAs. 35 % of the clusters extend beyond the annotated transcript; we find that these clusters correspond to, and are likely derived from, novel polyadenylated mRNA isoforms that contain previously unannotated extended 3’UTRs. Extended 3’ UTRs, and small RNAs derived from them, are also present in somatic tissues; a subset of these somatic 3’UTR small RNA clusters are absent in mice lacking MIWI2, indicating a role for MIWI2 in the metabolism of somatic small RNAs.

Conclusions

The finding that piRNAs are processed from extended 3’ UTRs suggests a role for piRNAs in the remodeling of 3’ UTRs. The presence of both clusters and extended 3’UTRs in somatic cells, with evidence for involvement of MIWI2, indicates that this pathway is more broadly distributed than currently appreciated.

【 授权许可】

   
2015 Yamtich et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

【 参考文献 】

• [1]Aravin A, Gaidatzis D, Pfeffer S, Lagos-Quintana M, Landgraf P, Iovino N, Morris P, Brownstein MJ, Kuramochi-Miyagawa S, Nakano T et al.. A novel class of small RNAs bind to MILI protein in mouse testes. Nature. 2006; 442(7099):203-207.
• [2]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.
• [3]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.
• [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]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.
• [6]Gunawardane LS, Saito K, Nishida KM, Miyoshi K, Kawamura Y, Nagami T, Siomi H, Siomi MC. A slicer-mediated mechanism for repeat-associated siRNA 5’ end formation in Drosophila. Science. 2007; 315(5818):1587-1590.
• [7]Aravin AA, Sachidanandam R, Bourc’his D, Schaefer C, Pezic D, Toth KF, Bestor T, Hannon GJ. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell. 2008; 31(6):785-799.
• [8]Grimson A, Srivastava M, Fahey B, Woodcroft BJ, Chiang HR, King N, Degnan BM, Rokhsar DS, Bartel DP. Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals. Nature. 2008; 455(7217):1193-1197.
• [9]Kuramochi-Miyagawa S, Watanabe T, Gotoh K, Totoki Y, Toyoda A, Ikawa M, Asada N, Kojima K, Yamaguchi Y, Ijiri TW et al.. DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev. 2008; 22(7):908-917.
• [10]Gou L-T, Dai P, Yang J-H, Xue Y, Hu Y-P, Zhou Y, Kang J-Y, Wang X, Li H, Hua M-M et al.. Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis. Cell Res. 2014; 24(6):680-700.
• [11]Watanabe T, Cheng E-c, Zhong M, Lin H. Retrotransposons and pseudogenes regulate mRNAs and lncRNAs via the piRNA pathway in the germline. Genome Res. 2015; 25(3)):368-380.
• [12]Zhang P, Kang JY, Gou LT, Wang J, Xue Y, Skogerboe G, Dai P, Huang DW, Chen R, Fu XD et al.. MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes. Cell Res. 2015; 25(2):193-207.
• [13]Li XZ, Roy CK, Dong X, Bolcun-Filas E, Wang J, Han BW, Xu J, Moore MJ, Schimenti JC, Weng Z et al.. An ancient transcription factor initiates the burst of pirna production during early meiosis in mouse testes. Mol Cell. 2013; 50(1):67-81.
• [14]Vourekas A, Zheng Q, Alexiou P, Maragkakis M, Kirino Y, Gregory BD, Mourelatos Z. Mili and Miwi target RNA repertoire reveals piRNA biogenesis and function of Miwi in spermiogenesis. Nat Struct Mol Biol. 2012; 19(8):773-781.
• [15]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.
• [16]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.
• [17]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.
• [18]Cui P, Lin Q, Zhang L, Ding F, Xin C, Zhang D, Sun F, Hu S, Yu J. The disequilibrium of nucleosomes distribution along chromosomes plays a functional and evolutionarily role in regulating gene expression. PLoS One. 2011; 6(8): Article ID e23219
• [19]Yan Z, Hu HY, Jiang X, Maierhofer V, Neb E, He L, Hu Y, Hu H, Li N, Chen W et al.. Widespread expression of piRNA-like molecules in somatic tissues. Nucleic Acids Res. 2011; 39(15):6596-6607.
• [20]Carmell MA, Girard A, van de Kant HJ, Bourc’his D, Bestor TH, de Rooij DG, Hannon GJ. MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev Cell. 2007; 12(4):503-514.
• [21]Juliano C, Wang J, Lin H. Uniting germline and stem cells: the function of Piwi proteins and the piRNA pathway in diverse organisms. Annu Rev Genet. 2011; 45:447-469.
• [22]Di Giammartino DC, Nishida K, Manley James L. Mechanisms and consequences of alternative polyadenylation. Mol Cell. 2011; 43(6):853-866.
• [23]Sandberg R, Neilson JR, Sarma A, Sharp PA, Burge CB. Proliferating cells express mRNAs with shortened 3’ untranslated regions and fewer microRNA target sites. Science. 2008; 320(5883):1643-1647.
• [24]Ji Z, Tian B. Reprogramming of 3’ untranslated regions of mRNAs by alternative polyadenylation in generation of pluripotent stem cells from different cell types. PLoS One. 2009; 4(12): Article ID e8419
• [25]Mayr C, Bartel DP. Widespread shortening of 3’UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell. 2009; 138(4):673-684.
• [26]Smibert P, Miura P, Westholm JO, Shenker S, May G, Duff MO, Zhang D, Eads BD, Carlson J, Brown JB et al.. Global patterns of tissue-specific alternative polyadenylation in Drosophila. Cell Rep. 2012; 1(3):277-289.
• [27]Jacobs JE, Wagner M, Dhahbi J, Boffelli D, Martin DI. Deficiency of MIWI2 (Piwil4) induces mouse erythroleukemia cell differentiation, but has no effect on hematopoiesis in vivo. PLoS One. 2013; 8(12):e82573.
• [28]Nolde MJ, Cheng EC, Guo S, Lin H. Piwi genes are dispensable for normal hematopoiesis in mice. PLoS One. 2013; 8(8):e71950.
• [29]Langmead B, Trapnell C, Pop M, Salzberg SL. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Bio. 2009; 10(3):R25. BioMed Central Full Text
• [30]Pavesi A, Conterio F, Bolchi A, Dieci G, Ottonello S. Identification of new eukaryotic tRNA genes in genomic DNA databases by a multistep weight matrix analysis of transcriptional control regions. Nucleic Acids Res. 1994; 22(7):1247-1256.
• [31]Eddy SR, Durbin R. RNA sequence analysis using covariance models. Nucleic Acids Res. 1994; 22(11):2079-2088.
• [32]Fichant GA, Burks C. Identifying potential tRNA genes in genomic DNA sequences. J Mol Biol. 1991; 220(3):659-671.
• [33]Lowe TM, Eddy SR. tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res. 1997; 25(5):955-964.
• [34]Chan PP, Lowe TM. GtRNAdb: a database of transfer RNA genes detected in genomic sequence. Nucleic Acids Res. 2009; 37(Database issue):D93-D97.
• [35]Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 2006; 34(34(Database issue)):D140-D144.
• [36]Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ. miRBase: tools for microRNA genomics. Nucleic Acids Res. 2008; 36(Database issue):D154-D158.
• [37]Weber MJ. New human and mouse microRNA genes found by homology search. FEBS J. 2005; 272(1):59-73.
• [38]Fujita PA, Rhead B, Zweig AS, Hinrichs AS, Karolchik D, Cline MS, Goldman M, Barber GP, Clawson H, Coelho A et al.. The UCSC genome browser database: update 2011. Nucleic Acids Res. 2011; 39(Database issue):D876-D882.
• [39]Griffiths-Jones S. The microRNA registry. Nucleic Acids Res. 2004; 32(Database issue):D109-D111.
• [40]Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 2011; 39(Database issue):D152-D157.
• [41]Flicek P, Amode MR, Barrell D, Beal K, Brent S, Carvalho-Silva D, Clapham P, Coates G, Fairley S, Fitzgerald S et al.. Ensembl 2012. Nucleic Acids Res. 2012; 40(Database issue):D84-D90.
• [42]Barrett T, Troup DB, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM et al.. NCBI GEO: archive for functional genomics data sets–10 years on. Nucleic Acids Res. 2011; 39(Database issue):D1005-D1010.
• [43]Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010; 26(6):841-842.
• [44]Jurka J, Kapitonov VV, Pavlicek A, Klonowski P, Kohany O, Walichiewicz J. Repbase Update, a database of eukaryotic repetitive elements. Cytogenet Genome Res. 2005; 110(1–4):462-467.
• [45]Kent WJ. BLAT–the BLAST-like alignment tool. Genome Res. 2002; 12(4):656-664.
• [46]Pruitt KD, Tatusova T, Maglott DR. NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res. 2005; 33(Database issue):D501-D504.
• [47]Boyle AP, Guinney J, Crawford GE, Furey TS. F-Seq: a feature density estimator for high-throughput sequence tags. Bioinformatics. 2008; 24(21):2537-2538.
• [48]da Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57.
• [49]da Huang W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009; 37(1):1-13.
• [50]Myers RM, Stamatoyannopoulos J, Snyder M, Dunham I, Hardison RC, Bernstein BE, Gingeras TR, Kent WJ, Birney E, Wold B et al.. A user’s guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol. 2011; 9(4):e1001046.
• [51]Robinson JT, Thorvaldsdottir H, Winckler W, Guttman M, Lander ES, Getz G, Mesirov JP. Integrative genomics viewer. Nat Biotechnol. 2011; 29(1):24-26.