Prediction of the structure of the common perimitochondrial localization signal of nuclear transcripts in yeast
Languages of publication
Many nuclear genes encoding mitochondrial proteins require specific localization of their mRNAs to the vicinity of mitochondria for proper expression. Studies in Saccharomyces cerevisiae have shown that the cis-acting signal responsible for subcellular localization of mRNAs is localized in the 3' UTR of the transcript. In this paper we present an in silico approach for prediction of a common perimitochondrial localization signal of nuclear transcripts encoding mitochondrial proteins. We computed a consensus structure for this signal by comparison of 3' UTR models for about 3000 yeast transcripts with known localization. Our studies show a short stem-loop structure which appears in most mRNAs localized to the vicinity of mitochondria. The degree of similarity of a given 3' UTR to our consensus structure strongly correlates with experimentally determined perimitochondrial localization of the mRNA, therefore we believe that the structure we predicted acts as a subcellular localization signal. Since our algorithm operates on structures, it seems to be more reliable than sequence-based algorithms. The good predictive value of our model is supported by statistical analysis.
- Caballero JJ, Giron MD, Vargas AM, Sevillano N, Suarez MD, Salto R (2004) AU-rich elements in the mRNA 3'-untranslated region of the rat receptor for advanced glycation end products and their relevance to mRNA stability. Biochem Biophys Res Commun 319: 247-255.
- Cherry JM, Ball C, Weng S, Juvik G, Schmidt R, Adler C, Dunn B, Dwight S, Riles L, Mortimer RK, Botstein D (1997) Genetic and physical maps of Saccharomyces cerevisiae. Nature 387: 67-73.
- Corral-Debrinski M, Blugeon C, Jacq C (2000) In yeast the 3'untranslated region or the presequence of ATM1 is required for the exclusive localization of its mRNA to the vicinity of mitochondria. Mol Cell Biol 20: 7881-7892.
- Gish W (1996-2003) WU-BLAST http://blastwustledu.
- Graber JH, Cantor CR, Mohr SC, Smith TF (1999) Genomic detection of new yeast pre-mRNA 3'-end-processing signals. Nucleic Acids Res 27: 888-894.
- Grafi G, Sela I, Galili G (1993) Translational regulation of human beta interferon mRNA: association of the 3' AU-rich sequence with the poly(A) tail reduces translation efficiency in vitro. Mol Cell Biol 13: 3487-3493.
- Higgins D, Thompson J, Gibson T, Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22: 4673-4680.
- Hofacker IL (2003) Vienna RNA secondary structure server Nucleic Acids Res 31: 3429-3431.
- Huh WK, Falvo JV, Gerke LC, Carroll AS, Howson RW, Weissman JS, O'Shea EK (2003) Global analysis of protein localization in budding yeast. Nature 425: 686-691.
- Jacobs Anderson JS, Parker R (2000) Computational identification of cis-acting elements affecting post-transcriptional control of gene expression in Saccharomyces cerevisiae. Nucleic Acids Res 28: 1604-1617.
- Jansen RP (2001) mRNA localization: message on the move. Nat Rev Mol Cell Biol 2: 247-256.
- Legendre M, Gautheret D (2003) Sequence determinants in human polyadenylation site selection. BMC Genomics 4: 7.
- Marc P, Margeot A, Devaux F, Blugeon C, Corral-Debrinski M, Jacq C (2002) Genome-wide analysis of mRNAs targeted to yeast mitochondria. EMBO Rep 3: 159-164.
- Margeot A, Blugeon C, Sylvestre J, Vialette S, Jacq C, Corral-Debrinski M (2002) In Saccharomyces cerevisiae ATP2 mRNA sorting to the vicinity of mitochondria is essential for respiratory function. EMBO J 21: 6893-6904.
- Pesole G, Liuni S, Grillo G, Licciulli F, Mignone F, Gissi C, Saccone C (2002) UTRdb and UTRsite: specialized databases of sequences and functional elements of 5' and 3' untranslated regions of eukaryotic mRNAs; Update 2002. Nucleic Acids Res 30: 335-340.
- Sylvestre J, Margeot A, Jacq C, Dujardin G, Corral-Debrinski M (2003) The role of the 3'untranslated region in mrna sorting to the vicinity of mitochondria is conserved from yeast to human cells. Mol Biol Cell 14: 3848-3856.
- Yamada M, Hayatsu N, Matsuura A, Ishikawa F (1998) Y'-Help1 a DNA helicase encoded by the yeast subtelomeric Y' element is induced in survivors defective for telomerase. J Biol Chem 273: 33360-33366.
- Zuker M (2003) Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31: 3406-3415.
Publication order reference