Analysis of Circular RNA in Caenorhabditis elegans

作者: 刘骏武 , 陈玲玲 :华中农业大学信息学院,湖北 武汉;

关键词: 外显子环状RNA线虫生长发育特异性内含子配对驱动环化Exonic Circular RNA C. elegans Developmental Specificity Intron-Pairing-Driven Circularization

外显子环状RNA (ecircRNA)是前体信使RNA中外显子经过反向剪接首尾相连而成环的一类特殊的RNA分子。近期多项研究发现,这类环状RNA广泛存在于真核生物细胞中,并具有调控基因表达的重要功能。本文根据线虫不同生长发育阶段的RNA测序数据,共预测出1112个典型的外显子环状RNA。对这些环状RNA进行分析,发现它们具有生长发育阶段特异性,并同线性的mRNA分子不具有直接的相关性。通过分析环状RNA侧翼内含子序列信息,证明在线虫中环状RNA的形成支持内含子配对驱动环化模型。

Abstract: Exonic circular RNA (ecircRNA) is a class of special RNA molecule which is processed from pre- mRNA through back-to-splice. Recently, a lot of researches identified thousands of circular RNA in eukaryotes and found that circRNA could function as gene regulator. In our research, we predicted 1112 canonical circular RNAs in RNase R treated RNA-seq from different development stages of Caenorhabditis elegans. We discovered that these circular RNAs had developmental specificity, and had no obvious correlation with linear RNA. Through analyzing the sequence information of flanking introns, we inferred that circular RNAs in C. elegans were produced by intron- pair-ing-driven circularization model.

文章引用: 刘骏武 , 陈玲玲 (2015) 线虫环状RNA分析。 计算生物学, 5, 17-28. doi: 10.12677/HJCB.2015.52003


[1] Nigro, J.M., Cho, K.R., Fearon, E.R., Kern, S.E., Ruppert, J.M., Oliner, J.D., Kinzler, K.W. and Vogelstein, B. (1991) Scrambled exons. Cell, 64, 607-613.

[2] Cocquerelle, C., Daubersies, P., Majerus, M.-A., Kerckaert, J.-P. and Bailleul, B. (1992) Splicing with inverted order of exons occurs proximal to large introns. The EMBO Journal, 11, 1095-1098.

[3] Capel, B., Swain, A., Nicolis, S., Hacker, A., Walter, M., Koopman, P., Goodfellow, P. and Lo-vell-Badge, R. (1993) Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell, 73, 1019-1030.

[4] Cocquerelle, C., Mascrez, B., Hetuin, D. and Bailleul, B. (1993) Mis-splicing yields circular RNA molecules. The FASEB Journal, 7, 155-160.

[5] Jeck, W.R., Sorrentino, J.A., Wang, K., Slevin, M.K., Burd, C.E., Liu, J., Marzluff, W.F. and Sharpless, N.E. (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA, 19, 141-157.

[6] Salzman, J., Chen, R.E., Olsen, M.N., Wang, P.L. and Brown, P.O. (2013) Cell-type specific features of circular RNA expression. PLoS Genet, 9, e1003777.

[7] Guo, J.U., Agarwal, V., Guo, H. and Bartel, D.P. (2014) Expanded identification and characterization of mammalian circular RNAs. Genome Biology, 15, 304-313.

[8] Memczak, S., Jens, M., Elefsinioti, A., Torti, F., Krueger, J., Rybak, A., Maier, L., Mackowiak, S.D., Gregersen, L.H., Munschauer, M., Loewer, A., Ziebold, U., Landthaler, M., Kocks, C., le Noble, F. and Rajewsky, N. (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature, 495, 333-338.

[9] Westholm, J.O., Miura, P., Olson, S., Shenker, S., Joseph, B., Sanfilippo, P., Celniker, S.E., Graveley, B.R. and Lai, E.C. (2014) Genome-wide analysis of drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation. Cell Reports, 9, 1966-1980.

[10] Danan, M., Schwartz, S., Edelheit, S. and Sorek, R. (2012) Transcriptome-wide discovery of circular RNAs in Archaea. Nucleic Acids Reserach, 40, 3131-3142.

[11] Hansen, T.B., Jensen, T.I., Clausen, B.H., Bramsen, J.B., Finsen, B., Damgaard, C.K. and Kjems, J. (2013) Natural RNA circles function as efficient microRNA sponges. Nature, 495, 384-388.

[12] Hansen, T.B., Wiklund, E.D., Bramsen, J.B., Villadsen, S.B., Statham, A.L., Clark, S.J. and Kjems, J. (2011) miRNA- dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. EMBO Journal, 30, 4414-4422.

[13] Li, Z., Huang, C., Bao, C., Chen, L., Lin, M., Wang, X., Zhong, G., Yu, B., Hu, W., Dai, L., Zhu, P., Chang, Z., Wu, Q., Zhao, Y., Jia, Y., Xu, P., Liu, H. and Shan, G. (2015) Exon-intron circular RNAs regulate transcription in the nucleus. Nature Structural Molecular Biology, 22, 256-264.

[14] Zhang, X.O. and Wang, H.B., Zhang, Y., Lu, X., Chen, L.L., Yang, L. (2014) Complementary sequence-mediated exon circularization. Cell, 159, 134-147.

[15] Liang, D. and Wilusz, J.E. (2014) Short intronic repeat sequences facilitate circular RNA production. Genes and Development, 28, 2233-2247.

[16] Ivanov, A., Memczak, S., Wyler, E., Torti, F., Porath, H.T., Orejuela, M.R., Piechotta, M., Levanon, E.Y., Landthaler, M., Dieterich, C. and Rajewsky, N. (2015) Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Reports, 10, 170-177.

[17] Kent, W.J., Sugnet, C.W., Furey, T.S., Roskin, K.M., Pringle, T.H., Zahler, A.M. and Haussler, D. (2002) The human genome browser at UCSC. Genome Research, 12, 996-1006.

[18] Kozomara, A. and Griffiths-Jones, S. (2014) miRBase: Annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Research, 42, D68-D73.

[19] Bolger, A.M., Lohse, M. and Usadel, B. (2014) Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics, 30, 2114-2120.

[20] Glažar, P., Papavasileiou, P. and Rajewsky, N. (2014) circBase: A database for circular RNAs. RNA, 20, 1666-1670.

[21] Trapnell, C., Roberts, A., Goff, L., Pertea, G., Kim, D., Kelley, D.R., Pimentel, H., Salzberg, S.L., Rinn, J.L. and Pachter, L. (2012) Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nature Protocols, 7, 562-578.

[22] Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R. and Salzberg, S.L. (2013) TopHat2: Accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biology, 14, R36.

[23] Mortazavi, A., Williams, B.A., McCue, K., Schaeffer, L. and Wold, B. (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nature Methods, 5, 621-628.

[24] Zhang, Y., Chen, D., Smith, M.A., Zhang, B. and Pan, X. (2012) Selection of reliable reference genes in Caenorhabditis elegans for analysis of nanotoxicity. PloS ONE, 7, e31849.

[25] Cheng, Z.-F. and Deutscher, M.P. (2005) An important role for RNase R in mRNA decay. Molecular Cell, 17, 313-318.

[26] Ye, J., Fang, L., Zheng, H., Zhang, Y., Chen, J., Zhang, Z., Wang, J., Li, S., Li, R. and Bolund, L. (2006) WEGO: A web tool for plotting GO annotations. Nucleic Acids Research, 34, W293-W297.

[27] You, X., Vlatkovic, I., Babic, A., Will, T., Epstein, I., Tushev, G., Akbalik, G., Wang, M., Glock, C., Quedenau, C., Wang, X., Hou, J., Liu, H., Sun, W., Sambandan, S., Chen, T., Schuman, E.M. and Chen, W. (2015) Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neuroscience, 18, 603-610.

[28] Gao, Y., Wang, J. and Zhao, F. (2015) CIRI: An efficient and unbiased algorithm for de novo circular RNA identification. Genome Biology, 16, 4.