Cytoplasmic Amplification of Transcriptional Noise Generates Substantial Cell-to-Cell Variability.

Cell Systems
Maike M K HansenLeor S Weinberger

Abstract

Transcription is an episodic process characterized by probabilistic bursts, but how the transcriptional noise from these bursts is modulated by cellular physiology remains unclear. Using simulations and single-molecule RNA counting, we examined how cellular processes influence cell-to-cell variability (noise). The results show that RNA noise is higher in the cytoplasm than the nucleus in ∼85% of genes across diverse promoters, genomic loci, and cell types (human and mouse). Measurements show further amplification of RNA noise in the cytoplasm, fitting a model of biphasic mRNA conversion between translation- and degradation-competent states. This multi-state translation-degradation of mRNA also causes substantial noise amplification in protein levels, ultimately accounting for ∼74% of intrinsic protein variability in cell populations. Overall, the results demonstrate how noise from transcriptional bursts is intrinsically amplified by mRNA processing, leading to a large super-Poissonian variability in protein levels.

References

Mar 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·B K FelberG N Pavlakis
Oct 6, 1997·Science·B Ossareh-NazariC Dargemont
Oct 22, 1998·Mathematical Biosciences·J E MittlerA S Perelson
Jul 28, 1999·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·M WatanabeE Nishida
Feb 5, 2000·Nature·N Barkai, S Leibler
Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·M Thattai, A van Oudenaarden
Apr 23, 2002·Nature Genetics·Ertugrul M OzbudakAlexander van Oudenaarden
Aug 17, 2002·Science·Michael B ElowitzPeter S Swain
Nov 15, 2002·Nature·Jeff HastyJ J Collins
Apr 3, 2003·Proceedings of the National Academy of Sciences of the United States of America·Michael L SimpsonGary S Sayler
Apr 11, 2003·Nature·William J BlakeJ J Collins
Jun 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Farren J IsaacsJ J Collins
May 5, 2004·PLoS Biology·Hunter B FraserMichael B Eisen
May 29, 2004·Science·Jonathan M Raser, Erin K O'Shea
Jul 6, 2004·Journal of Theoretical Biology·Michael L SimpsonGary S Sayler
May 11, 2005·Nature Reviews. Genetics·Mads KaernJames J Collins
Aug 9, 2005·Nature Genetics·Attila BecskeiAlexander van Oudenaarden
Nov 15, 2005·Nature Structural & Molecular Biology·Akio YamashitaAnn-Bin Shyu
Dec 20, 2005·Cell·Ido GoldingEdward C Cox
Dec 22, 2005·Nature Reviews. Genetics·Alfonso Martinez Arias, Penelope Hayward
Feb 3, 2006·Nature·D W AustinM L Simpson
May 23, 2006·Nature Genetics·Arren Bar-EvenNaama Barkai
Oct 20, 2006·PLoS Biology·Arjun RajSanjay Tyagi
Dec 26, 2006·Molecular Cell·William J BlakeJames J Collins
Jan 25, 2007·Nature Reviews. Molecular Cell Biology·Nicole L GarneauCarol J Wilusz
Mar 24, 2007·Science·Gürol M SüelMichael B Elowitz
Jun 16, 2007·Science·Hédia MaamarDavid Dubnau
Oct 24, 2007·The Journal of Cell Biology·Stéphanie BoireauEdouard Bertrand
Oct 30, 2008·Cell·Arjun Raj, Alexander van Oudenaarden
Nov 18, 2008·Nature Structural & Molecular Biology·Daniel ZenklusenRobert H Singer
Nov 6, 2009·Nature·Hubertus J E BeaumontPaul B Rainey
Dec 23, 2009·Physical Biology·Li-ping XiongLei-han Tang
Mar 19, 2011·Cell·Gábor BalázsiJames J Collins
May 3, 2011·PLoS Biology·Claire V HarperMichael R H White
Apr 14, 2012·Science·Brian MunskyAlexander van Oudenaarden
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona

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Citations

Jun 22, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Maike M K Hansen, Leor S Weinberger
May 23, 2019·Nature Reviews. Genetics·Nils ElingJohn C Marioni
Feb 12, 2020·Molecular Systems Biology·Robert Foreman, Roy Wollman
Dec 31, 2019·Molecular Systems Biology·Dhana FriedrichAlexander Loewer
Oct 24, 2019·Physical Review. E·Guillermo Rodrigo
May 3, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yan LiJoseph S Takahashi
Dec 6, 2019·Biochemical Society Transactions·Asli Azizoglu, Jörg Stelling
Feb 20, 2020·Physical Review. E·Luca CardelliAttila Csikasz-Nagy
Jul 8, 2020·Proceedings of the National Academy of Sciences of the United States of America·Sonali ChaturvediLeor S Weinberger
Nov 13, 2020·Physical Biology·Anissa Guillemin, Michael P H Stumpf
Mar 16, 2021·Molecular Systems Biology·Nicholas E PhillipsFelix Naef
May 30, 2020·Trends in Plant Science·Sandra Cortijo, James C W Locke
Apr 9, 2021·Science Advances·Yusuke OguchiHirofumi Shintaku
Jul 22, 2021·Molecular Systems Biology·Victor L BassKathryn Miller-Jensen

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