Abstract
Upstream open reading frames (uORFs) are open reading frames located within the 5’ UTR of an mRNA. It is believed that translated uORFs reduce the translational efficiency of the main coding region, and play an important role in gene regulation. However, only few uORFs are experimentally characterized. In this paper, we use ribosome footprinting together with a stacking-based classification approach to identify translated uORFs in Arabidopsis thaliana. Our approach resulted in a set of 5360 potentially translated uORFs in 2051 genes. GO terms enriched in uORF-containing genes include gene regulation, signal transduction and metabolic pathway. The identified uORFs occur with a higher frequency in multi-isoform genes, and many uORFs are affected by alternative transcript start sites or alternative splicing events.
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
Preview
Unable to display preview. Download preview PDF.
References
Morris, D.R., Geballe, A.P.: Upstream open reading frames as regulators of mRNA translation. Molecular and Cellular Biology 20, 8635–8642 (2000)
Calvo, S.E., Pagliarini, D.J., Mootha, V.K.: Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans. Proceedings of the National Academy of Sciences of the United States of America 106, 7507–7512 (2009)
Jeon, S., Kim, J.: Upstream open reading frames regulate the cell cycle-dependent expression of the RNA helicase Rok1 in Saccharomyces cerevisiae. FEBS Letters 584, 4593–4598 (2010)
Kim, B.H., Cai, X., Vaughn, J.N., von Arnim, A.G.: On the functions of the h subunit of eukaryotic initiation factor 3 in late stages of translation initiation. Genome Biology 8, R60 (2007)
von Arnim, A.G., Jia, Q., Vaughn, J.N.: Regulation of plant translation by upstream open reading frames. Plant Science: an International Journal of Experimental Plant Biology 214, 1–12 (2014)
Imai, A., Hanzawa, Y., Komura, M., Yamamoto, K.T., Komeda, Y., Takahashi, T.: The dwarf phenotype of the Arabidopsis acl5 mutant is suppressed by a mutation in an upstream ORF of a bHLH gene. Development 133, 3575–3585 (2006)
Alatorre-Cobos, F., Cruz-Ramirez, A., Hayden, C.A., Perez-Torres, C.A., Chauvin, A.L., Ibarra-Laclette, E., Alva-Cortes, E., Jorgensen, R.A., Herrera-Estrella, L.: Translational regulation of Arabidopsis XIPOTL1 is modulated by phosphocholine levels via the phylogenetically conserved upstream open reading frame 30. Journal of Experimental Botany 63, 5203–5221 (2012)
Ebina, I., Takemoto-Tsutsumi, M., Watanabe, S., Koyama, H., Endo, Y., Kimata, K., Igarashi, T., Murakami, K., Kudo, R., Ohsumi, A., Noh, A.L., Takahashi, H., Naito, S., Onouchi, H.: Identification of novel Arabidopsis thaliana upstream open reading frames that control expression of the main coding sequences in a peptide sequence-dependent manner. Nucleic Acids Research 43, 1562–1576 (2015)
Hanfrey, C., Franceschetti, M., Mayer, M.J., Illingworth, C., Michael, A.J.: Abrogation of upstream open reading frame-mediated translational control of a plant S-adenosylmethionine decarboxylase results in polyamine disruption and growth perturbations. The Journal of Biological Chemistry 277, 44131–44139 (2002)
Selpi, B.C.H., Kemp, G.J., Sarv, J., Kristiansson, E., Sunnerhagen, P.: Predicting functional upstream open reading frames in Saccharomyces cerevisiae. BMC Bioinformatics 10, 451 (2009)
Cvijovic, M., Dalevi, D., Bilsland, E., Kemp, G.J., Sunnerhagen, P.: Identification of putative regulatory upstream ORFs in the yeast genome using heuristics and evolutionary conservation. BMC Bioinformatics 8, 295 (2007)
Takahashi, H., Takahashi, A., Naito, S., Onouchi, H.: BAIUCAS: a novel BLAST-based algorithm for the identification of upstream open reading frames with conserved amino acid sequences and its application to the Arabidopsis thaliana genome. Bioinformatics 28, 2231–2241 (2012)
Ingolia, N.T., Ghaemmaghami, S., Newman, J.R., Weissman, J.S.: Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324, 218–223 (2009)
Fritsch, C., Herrmann, A., Nothnagel, M., Szafranski, K., Huse, K., Schumann, F., Schreiber, S., Platzer, M., Krawczak, M., Hampe, J., Brosch, M.: Genome-wide search for novel human uORFs and N-terminal protein extensions using ribosomal footprinting. Genome Research 22, 2208–2218 (2012)
Ingolia, N.T., Lareau, L.F., Weissman, J.S.: Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell 147, 789–802 (2011)
Trapnell, C., Pachter, L., Salzberg, S.L.: TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25, 1105–1111 (2009)
Andrews, S.J., Rothnagel, J.A.: Emerging evidence for functional peptides encoded by short open reading frames. Nat. Rev. Genet. 15, 193–204 (2014)
Vilela, C., McCarthy, J.E.: Regulation of fungal gene expression via short open reading frames in the mRNA 5’untranslated region. Molecular Microbiology 49, 859–867 (2003)
Juntawong, P., Girke, T., Bazin, J., Bailey-Serres, J.: Translational dynamics revealed by genome-wide profiling of ribosome footprints in Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America 111, E203–E212 (2014)
Saso Dzeroski, B.Z.: Is Combining Classifiers with Stacking Better than Selecting the Best One. Machine Learning 54, 255–273 (2004)
Wolpert, D.H.: Stacked generalization. Neural Networks 5, 241–259 (1992)
Rousseeuw, P.J.: Silhouettes: a Graphical Aid to the Interpretation and Validation of Cluster Analysis. Computational and Applied Mathematics, 53–65 (1987)
Du, Z., Zhou, X., Ling, Y., Zhang, Z., Su, Z.: agriGO: a GO analysis toolkit for the agricultural community. Nucleic Acids Research 38, W64–W70 (2010)
Tabuchi, T., Okada, T., Azuma, T., Nanmori, T., Yasuda, T.: Posttranscriptional regulation by the upstream open reading frame of the phosphoethanolamine N-methyltransferase gene. Bioscience, Biotechnology, and Biochemistry 70, 2330–2334 (2006)
Fawcett, T.: An introduction to ROC analysis. Pattern Recogn. Lett. 27, 861–874 (2006)
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this paper
Cite this paper
Hu, Q., Merchante, C., Stepanova, A.N., Alonso, J.M., Heber, S. (2015). A Stacking-Based Approach to Identify Translated Upstream Open Reading Frames in Arabidopsis Thaliana . In: Harrison, R., Li, Y., Măndoiu, I. (eds) Bioinformatics Research and Applications. ISBRA 2015. Lecture Notes in Computer Science(), vol 9096. Springer, Cham. https://doi.org/10.1007/978-3-319-19048-8_12
Download citation
DOI: https://doi.org/10.1007/978-3-319-19048-8_12
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-19047-1
Online ISBN: 978-3-319-19048-8
eBook Packages: Computer ScienceComputer Science (R0)