Abstract
The origin and evolution of small RNA molecules is a long-standing mystery. The protozoa represent the earliest eukaryotes and encompass rich diverse genetic resources. However, there are many contradictions and disputes prevalent in studies on protozoan microRNAs. In this review, we summarize the research on the analysis of small RNA transcriptome data on two representative protozoans, Trypanosoma brucei and Giardia lamblia , as generated by high throughput sequencing. The results show that these protozoans do not have canonical miRNAs. Unexpectedly, there are many types of endogenous small interfering RNAs (endo-siRNAs). In addition, stress induced tRNA derived small RNAs (sitRNAs) were observed in different life cycle stages of these parasites. In total, there are six kinds of sitRNAs in G. lamblia . These small RNAs are then found to be involved in the differentiation processes of primitive eukaryotes . These results showed that systematic analysis of small RNAs in the protozoa revealed a more complex picture than previously thought.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aravin AA, Hannon GJ (2008) Small RNA silencing pathways in germ and stem cells. In Cold Spring Harbor symposia on quantitative biology 73:283–290. doi:10.1101/sqb.2008.73.058
Arkhipova IR, Morrison HG (2001) Three retrotransposon families in the genome of Giardia lamblia: two telomeric, one dead. Proc Natl Acad Sci USA 98(25):14497–14502. doi:10.1073/pnas.231494798
Aslett M, Aurrecoechea C, Berriman M, Brestelli J, Brunk BP, Carrington M, Depledge DP, Fischer S, Gajria B, Gao X, Gardner MJ, Gingle A, Grant G, Harb OS, Heiges M, Hertz-Fowler C, Houston R, Innamorato F, Iodice J, Kissinger JC, Kraemer E, Li W, Logan FJ, Miller JA, Mitra S, Myler PJ, Nayak V, Pennington C, Phan I, Pinney DF, Ramasamy G, Rogers MB, Roos DS, Ross C, Sivam D, Smith DF, Srinivasamoorthy G, Stoeckert CJ, Jr., Subramanian S, Thibodeau R, Tivey A, Treatman C, Velarde G, Wang H (2010) TriTrypDB: a functional genomic resource for the Trypanosomatidae. Nucleic Acids Res 38 (Database issue):D457-462. doi:10.1093/nar/gkp851
Borsani O, Zhu J, Verslues PE, Sunkar R, Zhu JK (2005) Endogenous siRNAs derived from a pair of natural cis-antisense transcripts regulate salt tolerance in Arabidopsis. Cell 123(7):1279–1291. doi:10.1016/j.cell.2005.11.035
Braun L, Cannella D, Ortet P, Barakat M, Sautel CF, Kieffer S, Garin J, Bastien O, Voinnet O, Hakimi M-A (2010) A complex small RNA repertoire is generated by a plant/fungal-like machinery and effected by a metazoan-like Argonaute in the single-cell human parasite Toxoplasma gondii. PLoS Pathog 6:e1000920. doi:10.1371/journal.ppat.1000920
Cavalier-Smith T (2003) Protist phylogeny and the high-level classification of Protozoa. Eur J Protistol 39(4):338–348. doi:10.1078/0932-4739-00002
Chen Q, Yan M, Cao Z, Li X, Zhang Y, Shi J, Feng GH, Peng H, Zhang X, Zhang Y, Qian J, Duan E, Zhai Q, Zhou Q (2016) Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science 351(6271):397–400. doi:10.1126/science.aad7977
Chen XS, Collins LJ, Biggs PJ, Penny D (2009) High throughput genome-wide survey of small RNAs from the parasitic protists Giardia intestinalis and Trichomonas vaginalis. Genome Biol Evol 1:165–175. doi:10.1093/gbe/evp017
Chung WJ, Okamura K, Martin R, Lai EC (2008) Endogenous RNA interference provides a somatic defense against Drosophila transposons. Curr Biol CB 18(11):795–802. doi:10.1016/j.cub.2008.05.006
Czech B, Malone CD, Zhou R, Stark A, Schlingeheyde C, Dus M, Perrimon N, Kellis M, Wohlschlegel JA, Sachidanandam R, Hannon GJ, Brennecke J (2008) An endogenous small interfering RNA pathway in Drosophila. Nature 453(7196):798–802. doi:10.1038/nature07007
De S, Pal D, Ghosh SK (2006) Entamoeba histolytica: computational identification of putative microRNA candidates. Exp Parasitol 113(4):239–243. doi:10.1016/j.exppara.2006.01.009
Djikeng A, Shi HF, Tschudi C, Ullu E (2001) RNA interference in Trypanosoma brucei: Cloning of small interfering RNAs provides evidence for retroposon-derived 24-26-nucleotide RNAs. RNA 7(11):1522–1530
Ghildiyal M, Seitz H, Horwich MD, Li C, Du T, Lee S, Xu J, Kittler EL, Zapp ML, Weng Z, Zamore PD (2008) Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells. Science 320(5879):1077–1081. doi:10.1126/science.1157396
Goodarzi H, Liu X, Nguyen HC, Zhang S, Fish L, Tavazoie SF (2015) Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement. Cell 161(4):790–802. doi:10.1016/j.cell.2015.02.053
Gunasekera AM, Patankar S, Schug J, Eisen G, Kissinger J, Roos D, Wirth DF (2004) Widespread distribution of antisense transcripts in the Plasmodium falciparum genome. Mol Biochem Parasit 136(1):35–42. doi:10.1016/j.molbiopara.2004.02.007
Guo X, Zhang Z, Gerstein MB, Zheng D (2009) Small RNAs originated from pseudogenes: cis- or trans-acting? PLoS Comput Biol 5(7):e1000449. doi:10.1371/journal.pcbi.1000449
Ha M, Kim VN (2014) Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 15(8):509–524. doi:10.1038/nrm3838
Hao L, Cai P, Jiang N, Wang H, Chen Q (2010) Identification and characterization of microRNAs and endogenous siRNAs in Schistosoma japonicum. BMC Genom 11:55. doi:10.1186/1471-2164-11-55
Huang PJ, Lin WC, Chen SC, Lin YH, Sun CH, Lyu PC, Tang P (2012) Identification of putative miRNAs from the deep-branching unicellular flagellates. Genomics 99(2):101–107. doi:10.1016/j.ygeno.2011.11.002
Kawamura Y, Saito K, Kin T, Ono Y, Asai K, Sunohara T, Okada TN, Siomi MC, Siomi H (2008) Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells. Nature 453(7196):793–797. doi:10.1038/nature06938
Kolev NG, Tschudi C, Ullu E (2011) RNA interference in protozoan parasites: achievements and challenges. Eukaryot Cell 10(9):1156–1163. doi:10.1128/EC.05114-11
Li M, Belmonte JCI (2015) Roles for noncoding RNAs in cell-fate determination and regeneration. Nat Struct Mol Biol 22(1):2–4
Li ZH, Rana TM (2014) Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discovery 13(8):622–638. doi:10.1038/nrd4359
Li Y, Luo J, Zhou H, Liao JY, Ma LM, Chen YQ, Qu LH (2008) Stress-induced tRNA-derived RNAs: a novel class of small RNAs in the primitive eukaryote Giardia lamblia. Nucleic Acids Res 36(19):6048–6055. doi:10.1093/nar/gkn596
Li W, Saraiya AA, Wang CC (2011) Gene regulation in Giardia lamblia involves a putative microRNA derived from a small nucleolar RNA. PLoS Negl Trop Dis 5(10):e1338. doi:10.1371/journal.pntd.0001338
Li W, Saraiya AA, Wang CC (2012) The profile of snoRNA-derived microRNAs that regulate expression of variant surface proteins in Giardia lamblia. Cell Microbiol 14(9):1455–1473. doi:10.1111/j.1462-5822.2012.01811.x
Liao JY, Guo YH, Zheng LL, Li Y, Xu WL, Zhang YC, Zhou H, Lun ZR, Ayala FJ, Qu LH (2014) Both endo-siRNAs and tRNA-derived small RNAs are involved in the differentiation of primitive eukaryote Giardia lamblia. Proc Natl Acad Sci USA 111(39):14159–14164. doi:10.1073/pnas.1414394111
Lin WC, Li SC, Lin WC, Shin JW, Hu SN, Yu XM, Huang TY, Chen SC, Chen HC, Chen SJ, Huang PJ, Gan RRC, Chiu CH, Tang P (2009) Identification of microRNA in the protist Trichomonas vaginalis. Genomics 93(5):487–493. doi:10.1016/j.ygeno.2009.01.004
Lun ZR, Lai DH, Wen YZ, Zheng LL, Shen JL, Yang TB, Zhou WL, Qu LH, Hide G, Ayala FJ (2015) Cancer in the parasitic protozoans Trypanosoma brucei and Toxoplasma gondii. Proc Natl Acad Sci USA 112(29):8835–8842. doi:10.1073/pnas.1502599112
Macrae IJ, Zhou K, Li F, Repic A, Brooks AN, Cande WZ, Adams PD, Doudna JA (2006) Structural basis for double-stranded RNA processing by Dicer. Science 311(5758):195–198. doi:10.1126/science.1121638
Mallick B, Ghosh Z, Chakrabarti J (2008) MicroRNA switches in Trypanosoma brucei. Biochem Biophys Res Commun 372(3):459–463. doi:10.1016/j.bbrc.2008.05.084
Montagnes D, Roberts E, Lukes J, Lowe C (2012) The rise of model protozoa. Trends Microbiol 20(4):184–191. doi:10.1016/j.tim.2012.01.007
Nilsen TW (2008) Endo-siRNAs: yet another layer of complexity in RNA silencing. Nat Struct Mol Biol 15(6):546–548. doi:10.1038/nsmb0608-546
Obado SO, Taylor MC, Wilkinson SR, Bromley EV, Kelly JM (2005) Functional mapping of a Trypanosome centromere by chromosome fragmentation identifies a 16-kb GC-rich transcriptional “strand-switch” domain as a major feature. Genome Res 15(1):36–43. doi:10.1101/gr.2895105
Okamura K, Lai EC (2008) Endogenous small interfering RNAs in animals. Nat Rev Mol Cell Biol 9(9):673–678. doi:10.1038/nrm2479
Okamura K, Balla S, Martin R, Liu N, Lai EC (2008a) Two distinct mechanisms generate endogenous siRNAs from bidirectional transcription in Drosophila melanogaster. Nat Struct Mol Biol 15(6):581–590. doi:10.1038/nsmb.1438
Okamura K, Chung WJ, Ruby JG, Guo H, Bartel DP, Lai EC (2008b) The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs. Nature 453(7196):803–806. doi:10.1038/nature07015
Prucca CG, Slavin I, Quiroga R, Elias EV, Rivero FD, Saura A, Carranza PG, Lujan HD (2008) Antigenic variation in Giardia lamblia is regulated by RNA interference. Nature 456(7223):750–754. doi:10.1038/nature07585
Saraiya AA, Wang CC (2008) snoRNA, a novel precursor of microRNA in Giardia lamblia. PLoS Pathog 4(11):e1000224. doi:10.1371/journal.ppat.1000224
Saraiya AA, Li W, Wang CC (2011) A microRNA derived from an apparent canonical biogenesis pathway regulates variant surface protein gene expression in Giardia lamblia. RNA 17(12):2152–2164. doi:10.1261/rna.028118.111
Shan SW, Fang L, Shatseva T, Rutnam ZJ, Yang X, Du W, Lu WY, Xuan JW, Deng Z, Yang BB (2013) Mature miR-17-5p and passenger miR-17-3p induce hepatocellular carcinoma by targeting PTEN, GalNT7 and vimentin in different signal pathways. J Cell Sci 126(Pt 6):1517–1530. doi:10.1242/jcs.122895
Sharma U, Conine CC, Shea JM, Boskovic A, Derr AG, Bing XY, Belleannee C, Kucukural A, Serra RW, Sun F, Song L, Carone BR, Ricci EP, Li XZ, Fauquier L, Moore MJ, Sullivan R, Mello CC, Garber M, Rando OJ (2016) Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science 351(6271):391–396. doi:10.1126/science.aad6780
Sood P, Krek A, Zavolan M, Macino G, Rajewsky N (2006) Cell-type-specific signatures of microRNAs on target mRNA expression. Proc Natl Acad Sci USA 103(8):2746–2751. doi:10.1073/pnas.0511045103
Tam OH, Aravin AA, Stein P, Girard A, Murchison EP, Cheloufi S, Hodges E, Anger M, Sachidanandam R, Schultz RM, Hannon GJ (2008) Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 453(7194):534–538. doi:10.1038/nature06904
Tarver JE, Donoghue PC, Peterson KJ (2012) Do miRNAs have a deep evolutionary history? BioEssays News Rev Mol Cell Dev Biol 34(10):857–866. doi:10.1002/bies.201200055
Thorvaldsdottir H, Robinson JT, Mesirov JP (2013) Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Briefs Bioinform 14(2):178–192. doi:10.1093/bib/bbs017
Tschudi C, Shi H, Franklin JB, Ullu E (2012a) Small interfering RNA-producing loci in the ancient parasitic eukaryote Trypanosoma brucei. BMC Genom 13:427. doi:10.1186/1471-2164-13-427
Tschudi C, Shi H, Franklin JB, Ullu E (2012b) Small interfering RNA-producing loci in the ancient parasitic eukaryote Trypanosoma brucei. BMC Genom 13:427. doi:10.1186/1471-2164-13-427
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 (2008) Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 453(7194):539–543. doi:10.1038/nature06908
Wen YZ, Zheng LL, Liao JY, Wang MH, Wei Y, Guo XM, Qu LH, Ayala FJ, Lun ZR (2011) Pseudogene-derived small interference RNAs regulate gene expression in African Trypanosoma brucei. Proc Natl Acad Sci USA 108(20):8345–8350. doi:10.1073/pnas.1103894108
Wheeler BM, Heimberg AM, Moy VN, Sperling EA, Holstein TW, Heber S, Peterson KJ (2009) The deep evolution of metazoan microRNAs. Evol Dev 11(1):50–68. doi:10.1111/j.1525-142X.2008.00302.x
Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75(5):855–862
Wu C, Arora P (2014) MicroRNA passenger strand: orchestral symphony of paracrine signaling. Circ Cardiovas Genet 7(4):567–568. doi:10.1161/CIRCGENETICS.114.000805
Yang X, Du WW, Li H, Liu F, Khorshidi A, Rutnam ZJ, Yang BB (2013) Both mature miR-17-5p and passenger strand miR-17-3p target TIMP3 and induce prostate tumor growth and invasion. Nucleic Acids Res 41(21):9688–9704. doi:10.1093/nar/gkt680
Zhang Y, Liu XS, Liu QR, Wei LP (2006) Genome-wide in silico identification and analysis of cis natural antisense transcripts (cis-NATs) in ten species. Nucleic Acids Res 34(12):3465–3475. doi:10.1093/nar/gkl473
Zhang YQ, Chen DL, Tian HF, Zhang BH, Wen JF (2009) Genome-wide computational identification of microRNAs and their targets in the deep-branching eukaryote Giardia lamblia. Comput Biol Chem 33(5):391–396. doi:10.1016/j.compbiolchem.2009.07.013
Zheng LL, Wen YZ, Yang JH, Liao JY, Shao P, Xu H, Zhou H, Wen JZ, Lun ZR, Ayala FJ, Qu LH (2013) Comparative transcriptome analysis of small noncoding RNAs in different stages of Trypanosoma brucei. RNA 19(7):863–875. doi:10.1261/rna.035683.112
Zuker M (1989) On finding all suboptimal foldings of an RNA molecule. Science 244(4900):48–52
Acknowledgments
This work was supported by the grants from Ministry of Science and Technology of China; National Basic Research Program (No. 2011CB811300) from the National Basic Research program (“973” program) to L.-H.Q.; grants from the National Natural Science Foundation of China: 31401975 (to L.-L.Z.), 31401092 (to J.-Y.L.), 31301876 (to Y.-Z.W.), 31272305 and 31472058 (to Z.-R.L.) and 31471223 (to L.-H.Q.), and grants from Natural Science Foundation of Guangdong Province 2014A030313175 (to J.-Y.L.) and 2015A030311042 (to Z.-R.L). This was also supported in part by the Guangdong Province Key Laboratory of Computational Science and the Guangdong Province Computational Science Innovative Research Team. The authors declare no conflict of interest.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Zheng, LL., Liao, JY., Wen, YZ., Hide, G., Qu, LH., Lun, ZR. (2016). Different Types of Small RNAs in Protozoa. In: Leitão, A., Enguita, F. (eds) Non-coding RNAs and Inter-kingdom Communication. Springer, Cham. https://doi.org/10.1007/978-3-319-39496-1_11
Download citation
DOI: https://doi.org/10.1007/978-3-319-39496-1_11
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-39494-7
Online ISBN: 978-3-319-39496-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)