Single-Molecule Approaches to Stochastic Gene Expression

被引:253
作者
Raj, Arjun [1 ]
van Oudenaarden, Alexander [1 ]
机构
[1] MIT, Dept Phys, Cambridge, MA 02139 USA
关键词
single-molecule mRNA protein; gene expression noise; MESSENGER-RNA TRANSPORT; FLUCTUATING ENVIRONMENTS; TRANSCRIPTIONAL REGULATION; PROTEIN EXPRESSION; MAMMALIAN-CELLS; NOISE; LOCALIZATION; REVEALS; LEVEL; TIME;
D O I
10.1146/annurev.biophys.37.032807.125928
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Both the transcription of mRNAs from genes and their subsequent translation into proteins are inherently stochastic biochemical events, and this randomness can lead to substantial cell-to-cell variability in mRNA and protein numbers in otherwise identical cells. Recently, a number of studies have greatly enhanced our understanding of stochastic processes in gene expression by utilizing new methods capable of counting individual mRNAs and proteins in cells. In this review, we examine the insights that these studies have yielded in the field of stochastic gene expression. In particular, we discuss how these studies have played in understanding the properties of bursts in gene expression. We also compare the array of different methods that have arisen for single mRNA and protein detection, highlighting their relative strengths and weaknesses. In conclusion, we point out further areas where single-molecule techniques applied to gene expression may lead to new discoveries.
引用
收藏
页码:255 / 270
页数:16
相关论文
共 53 条
[1]   Enhancement of cellular memory by reducing stochastic transitions [J].
Acar, M ;
Becskei, A ;
van Oudenaarden, A .
NATURE, 2005, 435 (7039) :228-232
[2]   Stochastic switching as a survival strategy in fluctuating environments [J].
Acar, Murat ;
Mettetal, Jerome T. ;
van Oudenaarden, Alexander .
NATURE GENETICS, 2008, 40 (04) :471-475
[3]   Noise in protein expression scales with natural protein abundance [J].
Bar-Even, Arren ;
Paulsson, Johan ;
Maheshri, Narendra ;
Carmi, Miri ;
O'Shea, Erin ;
Pilpel, Yitzhak ;
Barkai, Naama .
NATURE GENETICS, 2006, 38 (06) :636-643
[4]   Localization and anchoring of mRNA in budding yeast [J].
Beach, DL ;
Salmon, ED ;
Bloom, K .
CURRENT BIOLOGY, 1999, 9 (11) :569-578
[5]   Gene expression profiling in single cells from the pancreatic islets of Langerhans reveals lognormal distribution of mRNA levels [J].
Bengtsson, M ;
Ståhlberg, A ;
Rorsman, P ;
Kubista, M .
GENOME RESEARCH, 2005, 15 (10) :1388-1392
[6]   Localization of ASH1 mRNA particles in living yeast [J].
Bertrand, E ;
Chartrand, P ;
Schaefer, M ;
Shenoy, SM ;
Singer, RH ;
Long, RM .
MOLECULAR CELL, 1998, 2 (04) :437-445
[7]   Stochastic protein expression in individual cells at the single molecule level [J].
Cai, L ;
Friedman, N ;
Xie, XS .
NATURE, 2006, 440 (7082) :358-362
[8]   Transcriptome-wide noise controls lineage choice in mammalian progenitor cells [J].
Chang, Hannah H. ;
Hemberg, Martin ;
Barahona, Mauricio ;
Ingber, Donald E. ;
Huang, Sui .
NATURE, 2008, 453 (7194) :544-U10
[9]   Transcriptional pulsing of a developmental gene [J].
Chubb, JR ;
Trcek, T ;
Shenoy, SM ;
Singer, RH .
CURRENT BIOLOGY, 2006, 16 (10) :1018-1025
[10]   Probing transcription factor dynamics at the single-molecule level in a living cell [J].
Elf, Johan ;
Li, Gene-Wei ;
Xie, X. Sunney .
SCIENCE, 2007, 316 (5828) :1191-1194