Universität zu Köln

Klironomos, Filippos D., de Meaux, Juliette ORCID: 0000-0002-2942-4750 and Berg, Johannes (2013). Can we always sweep the details of RNA-processing under the carpet? Phys. Biol., 10 (5). BRISTOL: IOP PUBLISHING LTD. ISSN 1478-3975

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Abstract

RNA molecules follow a succession of enzyme-mediated processing steps from transcription to maturation. The participating enzymes, for example the spliceosome for mRNAs and Drosha and Dicer for microRNAs, are also produced in the cell and their copy-numbers fluctuate over time. Enzyme copy-number changes affect the processing rate of the substrate molecules; high enzyme numbers increase the processing rate, while low enzyme numbers decrease it. We study different RNA-processing cascades where enzyme copy-numbers are either fixed or fluctuate. We find that for the fixed enzyme copy-numbers, the substrates at steady-state are Poisson-distributed, and the whole RNA cascade dynamics can be understood as a single birth-death process of the mature RNA product. In this case, solely fluctuations in the timing of RNA processing lead to variation in the number of RNA molecules. However, we show analytically and numerically that when enzyme copy-numbers fluctuate, the strength of RNA fluctuations increases linearly with the RNA transcription rate. This linear effect becomes stronger as the speed of enzyme dynamics decreases relative to the speed of RNA dynamics. Interestingly, we find that under certain conditions, the RNA cascade can reduce the strength of fluctuations in the expression level of the mature RNA product. Finally, by investigating the effects of processing polymorphisms, we show that it is possible for the effects of transcriptional polymorphisms to be enhanced, reduced or even reversed. Our results provide a framework to understand the dynamics of RNA processing.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klironomos, Filippos D. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Meaux, Juliette UNSPECIFIED orcid.org/0000-0002-2942-4750 UNSPECIFIED Berg, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-474782
DOI:	10.1088/1478-3975/10/5/056007
Journal or Publication Title:	Phys. Biol.
Volume:	10
Number:	5
Date:	2013
Publisher:	IOP PUBLISHING LTD
Place of Publication:	BRISTOL
ISSN:	1478-3975
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STOCHASTIC GENE-EXPRESSION; ARABIDOPSIS-THALIANA; MICRORNA BIOGENESIS; MAMMALIAN MICRORNAS; SIRNA BIOGENESIS; NONCODING RNAS; PLANTS; THRESHOLDS; INHIBITORS; NETWORKS Multiple languages Biochemistry & Molecular Biology; Biophysics Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47478