Transcriptional regulation is only half the story

News E-mail: email protected Molecular Systems Biology (2010)6:406https://doi.org/10.1038/msb.2010.63 PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures Wu et al, 2008), and it is preferable to analyses that are based on mRNA and protein measurements obtained from separate experiments. Nonetheless, this study is still limited to about 1000 soluble proteins, measured in an asynchronous, log-phase population of a tumor cell line, which contains chromosomal and methylation irregularities. Moreover, the strict separation of sequence features into those that determine steady-state mRNA levels and those that act post-transcriptionally is problematic: some nominally post-transcriptional features, such as those that influence ribosomal initiation, may feed back to influence steady-state mRNA levels as well (Iost and Dreyfus, 1995). Nonetheless, future studies in multiple cell lines, ideally including membrane proteins and synchronized populations, should elucidate how protein levels differ between and, indeed, define alternative cellular states. Such studies will be especially powerful when combined with high-throughput techniques for measuring ribosomal occupancy (Ingolia et al, 2009), allowing us to compare protein levels with direct estimates of translational efficiency, and to quantify protein stabilities as well. The quantification and analysis of protein levels for 1000 human genes is a remarkable technical feat and is emblematic of the system-wide approach to studying basic questions in molecular biology. Without doubt, the growing literature based on high-throughput mass spectroscopy will continue to inform our understanding of post-transcriptional regulation, much as microarrays revolutionized our understanding of transcriptional regulation. Such measurements performed in relatively natural cellular conditions on endogenous genes will nicely complement manipulative experiments that interrogate protein production using synthetic, heterologous gene constructs (e.g. Voges et al, 2004). Together, these systematic approaches promise to elucidate the operational details of Crick's central dogma. Conflict of Interest The author declares that he has no conflict of interest. References Brockmann R, Beyer A, Heinisch JJ, Wilhelm T (2007) Post-transcriptional expression regulation: what determines translation rates? PLoS Comput Biol 3: e57CrossrefCASPubMedWeb of Science®Google Scholar Ingolia NT, Ghaemmaghami S, Newman JR, Weissman JS (2009) Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324: 218–223CrossrefCASPubMedWeb of Science®Google Scholar Iost I, Dreyfus M (1995) The stability of Escherichia coli lacZ mRNA depends upon the simultaneity of its synthesis and translation. EMBO J 14: 3252–3261Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Lee TI, Rinaldi NJ, Robert F, Odom DT, Bar-Joseph Z, Gerber GK, Hannett NM, Harbison CT, Thompson CM, Simon I, Zeitlinger J, Jennings EG, Murray HL, Gordon DB, Ren B, Wyrick JJ, Tagne JB, Volkert TL, Fraenkel E, Gifford DK et al (2002) Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 298: 799–804CrossrefCASPubMedWeb of Science®Google Scholar Lu P, Vogel C, Wang R, Yao X, Marcotte EM (2007) Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation. Nat Biotechnol 25: 117–124CrossrefCASPubMedWeb of Science®Google Scholar Nie L, Wu G, Zhang W (2006) Correlation of mRNA expression and protein abundance affected by multiple sequence features related to translational efficiency in Desulfovibrio vulgaris: a quantitative analysis. Genetics 174: 2229–2243CrossrefCASPubMedWeb of Science®Google Scholar Schena M, Shalon D, Davis RW, Brown PO (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270: 467–470CrossrefCASPubMedWeb of Science®Google Scholar Vogel C, de Sousa RA, Ko D, Le S-H, Shapiro BA, Burns SC, Sandhu D, Boutz DR, Marcotte EM, Penalva LO (2010) Sequence signatures and mRNA concentration can explain two-thirds of protein abundance variation in a human cell line. Mol Syst Biol 6: 400Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Voges D, Watzele M, Nemetz C, Wizemann S, Buchberger B (2004) Analyzing and enhancing mRNA translational efficiency in an Escherichia coli in vitro expression system. Biochem Biophys Res Commun 318: 601–614CrossrefCASPubMedWeb of Science®Google Scholar Wu G, Nie L, Zhang W (2008) Integrative analyses of post-transcriptional regulation in the yeast Saccharomyces cerevisiae using transcriptomic and proteomic data. Curr Microbiol 57: 18–22CrossrefCASPubMedWeb of Science®Google Scholar Previous ArticleNext Article Volume 6Issue 11 January 2010In this issue FiguresReferencesRelatedDetailsLoading ...