The Hox cluster microRNA miR-615: a case study of intronic microRNA evolution

EvoDevo

Peter W. H. Holland¹  Shan Quah¹ 

[1] Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK

关键词: Intron;    Hoxc5;    Mammal;    miRNA;    Homeobox;   

Others  :  1228196
DOI  :  10.1186/s13227-015-0027-1

 received in 2015-08-31, accepted in 2015-09-25,  发布年份 2015

【 摘 要 】

Background

Introns represent a potentially rich source of existing transcription for the evolution of novel microRNAs (miRNAs). Within the Hox gene clusters, a miRNA gene, miR-615, is located within the intron of the Hoxc5 gene. This miRNA has a restricted phylogenetic distribution, providing an opportunity to examine the origin and evolution of a new miRNA within the intron of a developmentally-important homeobox gene.

Results

Alignment and structural analyses show that the sequence is highly conserved across eutherian mammals and absent in non-mammalian tetrapods. Marsupials possess a similar sequence which we predict will not be efficiently processed as a miRNA. Our analyses suggest that transcription of HOXC5 in humans is accompanied by expression of miR-615 in all cases, but that the miRNA can also be transcribed independently of its host gene through the use of an intragenic promoter. We present scenarios for the evolution of miR-615 through intronic exaptation, and speculate on the acquisition of independent transcriptional regulation. Target prediction and transcriptomic analyses suggest that the dominant product of miR-615 is involved in the regulation of growth and a range of developmental processes.

Conclusions

The miR-615 gene evolved within the intron of Hoxc5 in the ancestor of placental mammals. Using miR-615 as a case study, we propose a model by which a functional miRNA can emerge within an intron gradually, by selection on secondary structure followed by evolution of an independent miRNA promoter. The location within a Hox gene intron is of particular interest as the miRNA is specific to placental mammals, is co-expressed with its host gene and may share complementary functions.

【 授权许可】

   
2015 Quah and Holland.

【 图 表 】

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【 参考文献 】

• [1]Meunier J, Lemoine F, Soumillon M, Liechti A, Weier M, Guschanski K, Hu H, Khaitovich P, Kaessmann H, Meunier J, Lemoine F, Soumillon M, Liechti A, Weier M, Guschanski K, Hu H, Khaitovich P, Kaessmann H. Birth and expression evolution of mammalian microRNA genes. Genome Res. 2013; 23:34-45.
• [2]Campo-Paysaa F, Sémon M, Cameron RA, Peterson KJ, Schubert M. microRNA complements in deuterostomes origin and evolution of microRNAs. Evol Dev. 2011; 13:15-27.
• [3]Holland PWH. Evolution of homeobox genes. Wiley Interdiscip Rev Dev Biol. 2012; 2:31-45.
• [4]Tabin CJ. Why we have (only) five fingers per hand. Hox genes and the evolution of paired limbs. Development. 1992; 116:289-296.
• [5]Taguchi A, Kaku Y, Ohmori T, Sharmin S, Ogawa M, Sasaki H, Nishinakamura R. Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells. Cell Stem Cell. 2014; 14:53-67.
• [6]Patterson LT, Pembaur M, Potter SS. Hoxa11 and Hoxd11 regulate branching morphogenesis of the ureteric bud in the developing kidney. Development. 2001; 128:2153-2161.
• [7]Taylor HS, Vanden Heuvel GB, Igarashi P. A conserved Hox axis in the mouse and human female reproductive system. Late establishment and persistent adult expression of the Hoxa cluster genes. Biol Reprod. 1997; 57:1338-1345.
• [8]Tanzer A, Amemiya CT, Kim C-B, Stadler PF. Evolution of microRNAs located within Hox gene clusters. J Exp Zool B Mol Dev Evol. 2005; 304:75-85.
• [9]Candiani S. Focus on miRNAs evolution. a perspective from amphioxus. Brief Funct Genomics. 2012; 11:107-117.
• [10]Hui JHL, Marco A, Hunt S, Melling J, Griffiths-Jones S, Ronshaugen M. Structure, evolution and function of the bi-directionally transcribed iab-4/iab-8 microRNA locus in arthropods. Nucleic Acids Res. 2013; 41:3352-3361.
• [11]Woltering JM, Durston AJ. MiR-10 Represses HoxB1a and HoxB3a in Zebrafish. PLoS One. 2008; 3:e1396.
• [12]Baskerville S, Bartel DP. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA. 2005; 11:241-247.
• [13]Agranat-Tamir L, Shomron N, Sperling J, Sperling R. Interplay between pre-mRNA splicing and microRNA biogenesis within the supraspliceosome. Nucleic Acids Res. 2014; 42:4640-4651.
• [14]Quah S, Hui JHL, Holland PWH. A burst of miRNA innovation in the Early Evolution of Butterflies and Moths. Mol Biol Evol. 2015; 32:1161-1174.
• [15]Liang Y, Ridzon D, Wong L, Chen C. Characterization of microRNA expression profiles in normal human tissues. BMC Genom. 2007; 8:166. BioMed Central Full Text
• [16]Mi S, Lu J, Sun M, Li Z, Zhang H, Neilly MB, Wang Y, Qian Z, Jin J, Zhang Y, Bohlander SK, Le Beau MM, Larson RA, Golub TR, Rowley JD, Chen J. MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci USA. 2007; 104:19971-19976.
• [17]Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler AD. The Human genome browser at UCSC. Genome Res. 2002; 12:996-1006.
• [18]Flicek P, Amode MR, Barrell D, Beal K, Brent S, Carvalho-Silva D, Clapham P, Coates G, Fairley S, Fitzgerald S, Gil L, Gordon L, Hendrix M, Hourlier T, Johnson N, Käḧari AK, Keefe D, Keenan S, Komorowska M, Koscielny G, Kulesha E, Larsson P, Longden I, McLaren W, Muffato M, Overduin B, Pignatelli M, Pritchard B, Riat HS et al.. Ensembl 2012. Nucleic Acids Res. 2012; 42(D1):D749-D755.
• [19]Katoh K. MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res. 2002; 30:3059-3066.
• [20]Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, Yefanov A, Lee H, Zhang N, Robertson CL, Serova N, Davis S, Soboleva ANCBIGEO. Archive for functional genomics data sets—update. Nucleic Acids Res. 2013; 40(D1):D84-D90.
• [21]Chiang HR, Schoenfeld LW, Ruby JG, Auyeung VC, Spies N, Baek D, Johnston WK, Russ C, Luo S, Babiarz JE, Blelloch R, Schroth GP, Nusbaum C, Bartel DP. Mammalian microRNAs: experimental evaluation of novel and previously annotated genes. Genes Dev. 2010; 24:992-1009.
• [22]Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 2011; 39:D152-D157.
• [23]Kertesz M, Iovino N, Unnerstall U, Gaul U, Segal E. The role of site accessibility in microRNA target recognition. Nat Genet. 2007; 39:1278-1284.
• [24]UniProt: a hub for protein information. Nucleic Acids Res. 2014; 43:D204-D212.
• [25]Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson A, Kampf C, Sjostedt E, Asplund A, Olsson I, Edlund K, Lundberg E, Navani S, Szigyarto CA-K, Odeberg J, Djureinovic D, Takanen JO, Hober S, Alm T, Edqvist P-H, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk JM, Hamsten M, von Feilitzen K, Forsberg M et al.. Tissue-based map of the human proteome. Science. 2015; 347:1260419.
• [26]Katalin F-T, Soirova V, Sachidanandam R, Assaf G, Hannon GJ, Kapranov P, Foissac S, Willingham AT, Duttagupta R, Dumais E, Gingeras TR. Post-transcriptional processing generates a diversity of 5′-modified long and short RNAs. Nature. 2009; 457:1028-1032.
• [27]Zhang X-D, Zhang Y-H, Ling Y-H, Liu Y, Cao H-G, Yin Z-J, Ding J-P, Zhang X-R. Characterization and differential expression of microRNAs in the ovaries of pregnant and non-pregnant goats (Capra hircus). BMC Genom. 2013; 14:157. BioMed Central Full Text
• [28]Torley KJ, da Silveira JC, Smith P, Anthony RV, Veeramachaneni DNR, Winger QA, Bouma GJ. Expression of miRNAs in ovine fetal gonads: potential role in gonadal differentiation. Reprod Biol Endocrinol. 2011; 9:2. BioMed Central Full Text
• [29]Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F, Epstein CB, Frietze S, Harrow J, Kaul R, Khatun J, Lajoie BR, Landt SG, Lee B-K, Pauli F, Rosenbloom KR, Sabo P, Safi A, Sanyal A, Shoresh N, Simon JM, Song L, Trinklein ND, Altshuler RC, Birney E, Brown JB, Cheng C, Djebali S, Dong X, Dunham I et al.. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012; 489:57-74.
• [30]Artavanis-Tsakonas S. Notch signaling. Cell fate control and signal integration in development. Science. 1999; 284:770-776.
• [31]Yu H, Lindsay J, Feng Z-P, Frankenberg S, Hu Y, Carone D, Shaw G, Pask AJ, O’Neill R, Papenfuss AT, Renfree MB. Evolution of coding and non-coding genes in HOX clusters of a marsupial. BMC Genom. 2012; 13:251. BioMed Central Full Text
• [32]Warren WC, Hillier LW, Marshall Graves JA, Birney E, Ponting CP, Grützner F, Belov K, Miller W, Clarke L, Chinwalla AT, Yang S-P, Heger A, Locke DP, Miethke P, Waters PD, Veyrunes F, Fulton L, Fulton B, Graves T, Wallis J, Puente XS, López-Otín C, Ordóñez GR, Eichler EE, Chen L, Cheng Z, Deakin JE, Alsop A, Thompson K, Kirby P et al.. Genome analysis of the platypus reveals unique signatures of evolution. Nature. 2008; 453:175-183.
• [33]Axtell MJ, Westholm JO, Lai EC. Vive la différence. biogenesis and evolution of microRNAs in plants and animals. Genome Biol. 2011; 12:221. BioMed Central Full Text
• [34]Lyu Y, Shen Y, Li H, Chen Y, Guo L, Zhao Y, Hungate E, Shi S, Wu C-I, Tang T. New microRNAs in Drosophila–birth, death and cycles of adaptive evolution. PLoS Genet. 2014; 10:e1004096.
• [35]Zhou X, Ruan J, Wang G, Zhang W. Characterization and identification of microRNA core promoters in four model species. PLoS Comput Biol. 2007; 3(3):e37.
• [36]Gao W, Gu Y, Li Z, Cai H, Peng Q, Tu M, Kondo Y, Shinjo K, Zhu Y, Zhang J, Sekido Y, Han B, Qian Z, Miao Y. miR-615-5p is epigenetically inactivated and functions as a tumor suppressor in pancreatic ductal adenocarcinoma. Oncogene. 34(13):1629–40.
• [37]Carninci P, Sandelin A, Lenhard B, Katayama S, Shimokawa K, Ponjavic J, Semple CAM, Taylor MS, Engström PG, Frith MC, Forrest ARR, Alkema WB, Tan SL, Plessy C, Kodzius R, Ravasi T, Kasukawa T, Fukuda S, Kanamori-Katayama M, Kitazume Y, Kawaji H, Kai C, Nakamura M, Konno H, Nakano K, Mottagui-Tabar S, Arner P, Chesi A, Gustincich S, Persichetti F et al.. Genome-wide analysis of mammalian promoter architecture and evolution. Nat Genet. 2006; 38:626-635.
• [38]Frith MC, Valen E, Krogh A, Hayashizaki Y, Carninci P, Sandelin A. A code for transcription initiation in mammalian genomes. Genome Res. 2008; 18:1-12.
• [39]Brodsky AS, Meyer CA, Swinburne IA, Hall G, Keenan BJ, Liu XS, Fox EA, Silver PA. Genomic mapping of RNA polymerase II reveals sites of co-transcriptional regulation in human cells. Genome Biol. 2005; 6:R64. BioMed Central Full Text
• [40]Sandelin A, Carninci P, Lenhard B, Ponjavic J, Hayashizaki Y, Hume DA. Mammalian RNA polymerase II core promoters. insights from genome-wide studies. Nat Rev Genet. 2007; 8:424-436.
• [41]Suzuki S, Shaw G, Kaneko-Ishino T, Ishino F, Renfree MB. The evolution of mammalian genomic imprinting was accompanied by the acquisition of novel CpG islands. Genome Biol Evol. 2011; 3:1276-1283.
• [42]Backes C, Meese E, Lenhof HP, Keller A. A dictionary on microRNAs and their putative target pathways. Nucleic Acids Res. 2010; 38:4476-4486.
• [43]El Tayebi HM, Hosny KA, Esmat G, Breuhahn K, Abdelaziz AI. miR-615-5p is restrictedly expressed in cirrhotic and cancerous liver tissues and its overexpression alleviates the tumorigenic effects in hepatocellular carcinoma. FEBS Lett. 2012; 586:3309-3316.
• [44]Hulf T, Sibbritt T, Wiklund ED, Bert S, Strbenac D, Statham AL, Robinson MD, Clark SJ. Discovery pipeline for epigenetically deregulated miRNAs in cancer. integration of primary miRNA transcription. BMC Genom. 2011; 12:54. BioMed Central Full Text
• [45]Hoss AG, Kartha VK, Dong X, Latourelle JC, Dumitriu A, Hadzi TC, MacDonald ME, Gusella JF, Akbarian S, Chen J-F, Weng Z, Myers RH. MicroRNAs located in the Hox gene clusters are implicated in Huntington’s disease pathogenesis. PLoS Genet. 2014; 10:e1004188.
• [46]Bar M, Wyman SK, Fritz BR, Qi J, Garg KS, Parkin RK, Kroh EM, Bendoraite A, Mitchell PS, Nelson AM, Ruzzo WL, Ware C, Radich JP, Gentleman R, Ruohola-Baker H, Tewari M. MicroRNA discovery and profiling in human embryonic stem cells by deep sequencing of small RNA libraries. Stem Cells. 2008; 26:2496-2505.
• [47]Deschamps J, van Nes J. Developmental regulation of the Hox genes during axial morphogenesis in the mouse. Development. 2005; 132:2931-2942.
• [48]Ahn HW, Morin RD, Zhao H, Harris RA, Coarfa C, Chen ZJ, Milosavljevic A, Marra MA, Rajkovic A. MicroRNA transcriptome in the newborn mouse ovaries determined by massive parallel sequencing. Mol Hum Reprod. 2010; 16:463-471.
• [49]Vainio S, Lin Y. Coordinating early kidney development. lessons from gene targeting. Nat Rev Genet. 2002; 3:533-543.
• [50]Wellik DM. Hox genes and kidney development. Pediatr Nephrol. 2011; 26:1559-1565.
• [51]Ross AJ, Capel B. Signaling at the crossroads of gonad development. Trends Endocrinol Metab. 2005; 16(1):19-25.
• [52]Wanek N, Muneoka K, Holler-Dinsmore G, Burton R, Bryant SV. A staging system for mouse limb development. J Exp Zool. 1989; 249:41-49.