Transcriptional Control of Apical-Basal Polarity Regulators

Cell polarity is essential for many functions of cells and tissues including the initial establishment and subsequent maintenance of epithelial tissues, asymmetric cell division, and morphogenetic movements. Cell polarity along the apical-basal axis is controlled by three protein complexes that interact with and co-regulate each other: The Par-, Crumbs-, and Scrib-complexes. The localization and activity of the components of these complexes is predominantly controlled by protein-protein interactions and protein phosphorylation status. Increasing evidence accumulates that, besides the regulation at the protein level, the precise expression control of polarity determinants contributes substantially to cell polarity regulation. Here we review how gene expression regulation influences processes that depend on the induction, maintenance, or abolishment of cell polarity with a special focus on epithelial to mesenchymal transition and asymmetric stem cell division. We conclude that gene expression control is an important and often neglected mechanism in the control of cell polarity.

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Methods for the analysis of transcriptome dynamics

Toxicology Research ◽

10.1039/c9tx00088g ◽

2019 ◽

Vol 8 (5) ◽

pp. 597-612 ◽

Cited By ~ 2

Author(s):

Daniela F. Rodrigues ◽

Vera M. Costa ◽

Ricardo Silvestre ◽

Maria L. Bastos ◽

Félix Carvalho

Keyword(s):

Gene Expression ◽

Transcriptome Analysis ◽

Messenger Rna ◽

Noncoding Rna ◽

Gene Expression Regulation ◽

System Level ◽

Rna Transcription ◽

Expression Control ◽

Gene Expression Control ◽

Gene Expression Alterations

Abstract The transcriptome is the complete set of transcripts in a cell or tissue and includes ribosomal RNA (rRNA), messenger RNA (mRNA), transfer RNA (tRNA), and regulatory noncoding RNA. At steady-state, the transcriptome results from a compensatory variation of the transcription and decay rate to maintain the RNA concentration constant. RNA transcription constitutes the first stage in gene expression, and thus is a major and primary mode of gene expression control. Nevertheless, regulation of RNA decay is also a key factor in gene expression control, involving either selective RNA stabilization or enhanced degradation. Transcriptome analysis allows the identification of gene expression alterations, providing new insights regarding the pathways and mechanisms involved in physiological and pathological processes. Upon perturbation of cell homeostasis, rapid changes in gene expression are required to adapt to new conditions. Thus, to better understand the regulatory mechanisms associated with gene expression alterations, it is vital to acknowledge the relative contribution of RNA synthesis and decay to the transcriptome. To the toxicology field, the study of gene expression regulation mechanisms can help identify the early and mechanistic relevant cellular events associated with a particular response. This review aims to provide a critical comparison of the available methods used to analyze the contribution of RNA transcription and decay to gene expression dynamics. Notwithstanding, an integration of the data obtained is necessary to understand the entire repercussions of gene transcription changes at a system-level. Thus, a brief overview of the methods available for the integration and analysis of the data obtained from transcriptome analysis will also be provided.

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Pat1 proteins: a life in translation, translation repression and mRNA decay

Biochemical Society Transactions ◽

10.1042/bst0381602 ◽

2010 ◽

Vol 38 (6) ◽

pp. 1602-1607 ◽

Cited By ~ 34

Author(s):

Aline Marnef ◽

Nancy Standart

Keyword(s):

Gene Expression ◽

Transcriptional Control ◽

Mrna Decay ◽

Current Knowledge ◽

Translational Repression ◽

Processing Bodies ◽

P Bodies ◽

Expression Control ◽

Gene Expression Control ◽

Sequential Binding

Pat1 proteins are conserved across eukaryotes. Vertebrates have evolved two Pat1 proteins paralogues, whereas invertebrates and yeast only possess one such protein. Despite their lack of known domains or motifs, Pat1 proteins are involved in several key post-transcriptional mechanisms of gene expression control. In yeast, Pat1p interacts with translating mRNPs (messenger ribonucleoproteins), and is responsible for translational repression and decapping activation, ultimately leading to mRNP degradation. Drosophila HPat and human Pat1b (PatL1) proteins also have conserved roles in the 5′→3′ mRNA decay pathway. Consistent with their functions in silencing gene expression, Pat1 proteins localize to P-bodies (processing bodies) in yeast, Drosophila, Caenorhabditis elegans and human cells. Altogether, Pat1 proteins may act as scaffold proteins allowing the sequential binding of repression and decay factors on mRNPs, eventually leading to their degradation. In the present mini-review, we present the current knowledge on Pat1 proteins in the context of their multiple functions in post-transcriptional control.

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Faculty Opinions recommendation of Global quantification of mammalian gene expression control.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.10925958.12978054 ◽

2011 ◽

Author(s):

Jürg Bahler

Keyword(s):

Gene Expression ◽

Mammalian Gene ◽

Expression Control ◽

Gene Expression Control ◽

Mammalian Gene Expression

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Faculty Opinions recommendation of Global quantification of mammalian gene expression control.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.10925958.12716054 ◽

2011 ◽

Author(s):

Luc DesGroseillers ◽

Karine Boulay

Keyword(s):

Gene Expression ◽

Mammalian Gene ◽

Expression Control ◽

Gene Expression Control ◽

Mammalian Gene Expression

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High-performance chemical- and light-inducible recombinases in mammalian cells and mice

Nature Communications ◽

10.1038/s41467-019-12800-7 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 9

Author(s):

Benjamin H. Weinberg ◽

Jang Hwan Cho ◽

Yash Agarwal ◽

N. T. Hang Pham ◽

Leidy D. Caraballo ◽

...

Keyword(s):

Gene Expression ◽

Mammalian Cells ◽

High Performance ◽

Genome Engineering ◽

Genetic Circuits ◽

Control Of Gene Expression ◽

Expression Control ◽

Gene Expression Control ◽

High Performance Systems ◽

Spatiotemporal Control

Abstract Site-specific DNA recombinases are important genome engineering tools. Chemical- and light-inducible recombinases, in particular, enable spatiotemporal control of gene expression. However, inducible recombinases are scarce due to the challenge of engineering high performance systems, thus constraining the sophistication of genetic circuits and animal models that can be created. Here we present a library of >20 orthogonal inducible split recombinases that can be activated by small molecules, light and temperature in mammalian cells and mice. Furthermore, we engineer inducible split Cre systems with better performance than existing systems. Using our orthogonal inducible recombinases, we create a genetic switchboard that can independently regulate the expression of 3 different cytokines in the same cell, a tripartite inducible Flp, and a 4-input AND gate. We quantitatively characterize the inducible recombinases for benchmarking their performances, including computation of distinguishability of outputs. This library expands capabilities for multiplexed mammalian gene expression control.

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