Transcriptome and proteome quantification of a tumor model provides novel insights into post-transcriptional gene regulation

被引:41
作者
Jueschke, Christoph [1 ]
Dohnal, Ilse [2 ]
Pichler, Peter [2 ,3 ]
Harzer, Heike [1 ]
Swart, Remco [4 ]
Ammerer, Gustav [2 ]
Mechtler, Karl [1 ,3 ]
Knoblich, Juergen A. [1 ]
机构
[1] Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria
[2] Christian Doppler Lab Proteome Anal, A-1030 Vienna, Austria
[3] Res Inst Mol Pathol IMP, A-1030 Vienna, Austria
[4] Thermo Fisher Sci, NL-1046 AA Amsterdam, Netherlands
来源
GENOME BIOLOGY | 2013年 / 14卷 / 11期
基金
欧洲研究理事会; 奥地利科学基金会;
关键词
NEURAL STEM-CELLS; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER; MASS-SPECTROMETRY; RNA-SEQ; MESSENGER-RNA; SELF-RENEWAL; BRAIN-TUMOR; QUANTITATIVE PROTEOMICS; EXPRESSION LEVELS;
D O I
10.1186/gb-2013-14-11-r133
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Genome-wide transcriptome analyses have given systems-level insights into gene regulatory networks. Due to the limited depth of quantitative proteomics, however, our understanding of post-transcriptional gene regulation and its effects on protein-complex stoichiometry are lagging behind. Results: Here, we employ deep sequencing and the isobaric tag for relative and absolute quantification (iTRAQ) technology to determine transcript and protein expression changes of a Drosophila brain tumor model at near genome-wide resolution. In total, we quantify more than 6,200 tissue-specific proteins, corresponding to about 70% of all transcribed protein-coding genes. Using our integrated data set, we demonstrate that post-transcriptional gene regulation varies considerably with biological function and is surprisingly high for genes regulating transcription. We combine our quantitative data with protein-protein interaction data and show that post-transcriptional mechanisms significantly enhance co-regulation of protein-complex subunits beyond transcriptional co-regulation. Interestingly, our results suggest that only about 11% of the annotated Drosophila protein complexes are co-regulated in the brain. Finally, we refine the composition of some of these core protein complexes by analyzing the co-regulation of potential subunits. Conclusions: Our comprehensive transcriptome and proteome data provide a valuable resource for quantitative biology and offer novel insights into understanding post-transcriptional gene regulation in a tumor model.
引用
收藏
页数:20
相关论文
共 79 条
[41]   High Precision Quantitative Proteomics Using iTRAQ on an LTQ Orbitrap: A New Mass Spectrometric Method Combining the Benefits of All [J].
Koecher, Thomas ;
Pichler, Peter ;
Schutzbier, Michael ;
Stingl, Christoph ;
Kaul, Axel ;
Teucher, Nils ;
Hasenfuss, Gerd ;
Penninger, Josef M. ;
Mechtler, Karl .
JOURNAL OF PROTEOME RESEARCH, 2009, 8 (10) :4743-4752
[42]   Coupling and coordination in gene expression processes: a systems biology view [J].
Komili, Suzanne ;
Silver, Pamela A. .
NATURE REVIEWS GENETICS, 2008, 9 (01) :38-48
[43]   A SIMPLE METHOD FOR DISPLAYING THE HYDROPATHIC CHARACTER OF A PROTEIN [J].
KYTE, J ;
DOOLITTLE, RF .
JOURNAL OF MOLECULAR BIOLOGY, 1982, 157 (01) :105-132
[44]   Selected reaction monitoring for quantitative proteomics: a tutorial [J].
Lange, Vinzenz ;
Picotti, Paola ;
Domon, Bruno ;
Aebersold, Ruedi .
MOLECULAR SYSTEMS BIOLOGY, 2008, 4 (1)
[45]   Ultrafast and memory-efficient alignment of short DNA sequences to the human genome [J].
Langmead, Ben ;
Trapnell, Cole ;
Pop, Mihai ;
Salzberg, Steven L. .
GENOME BIOLOGY, 2009, 10 (03)
[46]   A dynamic model of proteome changes reveals new roles for transcript alteration in yeast [J].
Lee, M. Violet ;
Topper, Scott E. ;
Hubler, Shane L. ;
Hose, James ;
Wenger, Craig D. ;
Coon, Joshua J. ;
Gasch, Audrey P. .
MOLECULAR SYSTEMS BIOLOGY, 2011, 7
[47]   Transcriptional signature of an adult brain tumor in Drosophila -: art. no. 24 [J].
Loop, T ;
Leemans, R ;
Stiefel, U ;
Hermida, L ;
Egger, B ;
Xie, FK ;
Primig, M ;
Certa, U ;
Fischbach, KF ;
Reichert, H ;
Hirth, F .
BMC GENOMICS, 2004, 5 (1)
[48]   Defining the transcriptome and proteome in three functionally different human cell lines [J].
Lundberg, Emma ;
Fagerberg, Linn ;
Klevebring, Daniel ;
Matic, Ivan ;
Geiger, Tamar ;
Cox, Juergen ;
Algenas, Cajsa ;
Lundeberg, Joakim ;
Mann, Matthias ;
Uhlen, Mathias .
MOLECULAR SYSTEMS BIOLOGY, 2010, 6
[49]   Quantification of mRNA and protein and integration with protein turnover in a bacterium [J].
Maier, Tobias ;
Schmidt, Alexander ;
Gueell, Marc ;
Kuehner, Sebastian ;
Gavin, Anne-Claude ;
Aebersold, Ruedi ;
Serrano, Luis .
MOLECULAR SYSTEMS BIOLOGY, 2011, 7
[50]   Correlation of mRNA and protein in complex biological samples [J].
Maier, Tobias ;
Guell, Marc ;
Serrano, Luis .
FEBS LETTERS, 2009, 583 (24) :3966-3973