The role of alternative Polyadenylation in regulation of rhythmic gene expression

Natalia Ptitsyna, Sabri Boughorbel, Mohammed El Anbari, Andrey Ptitsyn

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Alternative transcription is common in eukaryotic cells and plays important role in regulation of cellular processes. Alternative polyadenylation results from ambiguous PolyA signals in 3' untranslated region (UTR) of a gene. Such alternative transcripts share the same coding part, but differ by a stretch of UTR that may contain important functional sites. Methods: The methodoogy of this study is based on mathematical modeling, analytical solution, and subsequent validation by datamining in multiple independent experimental data from previously published studies. Results: In this study we propose a mathematical model that describes the population dynamics of alternatively polyadenylated transcripts in conjunction with rhythmic expression such as transcription oscillation driven by circadian or metabolic oscillators. Analysis of the model shows that alternative transcripts with different turnover rates acquire a phase shift if the transcript decay rate is different. Difference in decay rate is one of the consequences of alternative polyadenylation. Phase shift can reach values equal to half the period of oscillation, which makes alternative transcripts oscillate in abundance in counter-phase to each other. Since counter-phased transcripts share the coding part, the rate of translation becomes constant. We have analyzed a few data sets collected in circadian timeline for the occurrence of transcript behavior that fits the mathematical model. Conclusion: Alternative transcripts with different turnover rate create the effect of rectifier. This "molecular diode" moderates or completely eliminates oscillation of individual transcripts and stabilizes overall protein production rate. In our observation this phenomenon is very common in different tissues in plants, mice, and humans. The occurrence of counter-phased alternative transcripts is also tissue-specific and affects functions of multiple biological pathways. Accounting for this mechanism is important for understanding the natural and engineering the synthetic cellular circuits.

Original languageEnglish
Article number576
JournalBMC Genomics
Volume18
Issue number1
DOIs
Publication statusPublished - 4 Aug 2017

Fingerprint

Polyadenylation
Gene Expression Regulation
Theoretical Models
Cell Engineering
Untranslated Regions
Population Dynamics
3' Untranslated Regions
Eukaryotic Cells
Observation
Genes
Proteins
TimeLine
Datasets

Keywords

  • Alternative transcription
  • Cellular circuits
  • Molecular diode, mathematical modeling, datamining
  • Oscillatory gene expression

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

The role of alternative Polyadenylation in regulation of rhythmic gene expression. / Ptitsyna, Natalia; Boughorbel, Sabri; El Anbari, Mohammed; Ptitsyn, Andrey.

In: BMC Genomics, Vol. 18, No. 1, 576, 04.08.2017.

Research output: Contribution to journalArticle

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