Available for a limited time only: Regulating gene expression through mRNA turnover

2014 ◽  
Vol 34 ◽  
pp. 1
Author(s):  
Imed Eddine Gallouzi ◽  
Christopher von Roretz
Keyword(s):  
Gene Expression ◽  
Mrna Turnover ◽  
Limited Time

scholarly journals Nucleoporin TPR is an integral component of the TREX-2 mRNA export pathway

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Vasilisa Aksenova ◽  
Alexandra Smith ◽  
Hangnoh Lee ◽  
Prasanna Bhat ◽  
Caroline Esnault ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Export ◽  
Mrna Turnover ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Nucleocytoplasmic Trafficking ◽  
Cellular Functions ◽  
Pore Complexes ◽  
Slow Turnover

Abstract Nuclear pore complexes (NPCs) are important for cellular functions beyond nucleocytoplasmic trafficking, including genome organization and gene expression. This multi-faceted nature and the slow turnover of NPC components complicates investigations of how individual nucleoporins act in these diverse processes. To address this question, we apply an Auxin-Induced Degron (AID) system to distinguish roles of basket nucleoporins NUP153, NUP50 and TPR. Acute depletion of TPR causes rapid and pronounced changes in transcriptomic profiles. These changes are dissimilar to shifts observed after loss of NUP153 or NUP50, but closely related to changes caused by depletion of mRNA export receptor NXF1 or the GANP subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex. Moreover, TPR depletion disrupts association of TREX-2 subunits (GANP, PCID2, ENY2) to NPCs and results in abnormal RNA transcription and export. Our findings demonstrate a unique and pivotal role of TPR in gene expression through TREX-2- and/or NXF1-dependent mRNA turnover.

scholarly journals Interrogating the degradation pathways of unstable mRNAs with XRN1-resistant sequences

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Volker Boehm ◽  
Jennifer V. Gerbracht ◽  
Marie-Charlotte Marx ◽  
Niels H. Gehring
Keyword(s):  
Gene Expression ◽  
Mrna Decay ◽  
Mrna Degradation ◽  
Eukaryotic Cells ◽  
Mrna Turnover ◽  
Degradation Pathways ◽  
Messenger Rnas ◽  
Endonucleolytic Cleavage ◽  
Nonsense Mediated Mrna Decay ◽  
Cytokine Mrnas

Abstract The turnover of messenger RNAs (mRNAs) is a key regulatory step of gene expression in eukaryotic cells. Due to the complexity of the mammalian degradation machinery, the contribution of decay factors to the directionality of mRNA decay is poorly understood. Here we characterize a molecular tool to interrogate mRNA turnover via the detection of XRN1-resistant decay fragments (xrFrag). Using nonsense-mediated mRNA decay (NMD) as a model pathway, we establish xrFrag analysis as a robust indicator of accelerated 5′–3′ mRNA decay. In tethering assays, monitoring xrFrag accumulation allows to distinguish decapping and endocleavage activities from deadenylation. Moreover, xrFrag analysis of mRNA degradation induced by miRNAs, AU-rich elements (AREs) as well as the 3′ UTRs of cytokine mRNAs reveals the contribution of 5′–3′ decay and endonucleolytic cleavage. Our work uncovers formerly unrecognized modes of mRNA turnover and establishes xrFrag as a powerful tool for RNA decay analyses.

scholarly journals Dynamic profiling of mRNA turnover reveals gene-specific and system-wide regulation of mRNA decay

2011 ◽  
Vol 22 (15) ◽  
pp. 2787-2795 ◽  
Author(s):  
Sarah E. Munchel ◽  
Ryan K. Shultzaberger ◽  
Naoki Takizawa ◽  
Karsten Weis
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Mrna Decay ◽  
Global Analysis ◽  
Decay Rates ◽  
Mrna Turnover ◽  
Control Of Gene Expression ◽  
Mrna Stabilization ◽  
Highly Sensitive ◽  
Wide Range

RNA levels are determined by the rates of both transcription and decay, and a mechanistic understanding of the complex networks regulating gene expression requires methods that allow dynamic measurements of transcription and decay in living cells with minimal perturbation. Here, we describe a metabolic pulse-chase labeling protocol using 4-thiouracil combined with large-scale RNA sequencing to determine decay rates of all mRNAs in Saccharomyces cerevisiae. Profiling in various growth and stress conditions reveals that mRNA turnover is highly regulated both for specific groups of transcripts and at the system-wide level. For example, acute glucose starvation induces global mRNA stabilization but increases the degradation of all 132 detected ribosomal protein mRNAs. This effect is transient and can be mimicked by inhibiting the target-of-rapamycin kinase. Half-lives of mRNAs critical for galactose (GAL) metabolism are also highly sensitive to changes in carbon source. The fast reduction of GAL transcripts in glucose requires their dramatically enhanced turnover, highlighting the importance of mRNA decay in the control of gene expression. The approach described here provides a general platform for the global analysis of mRNA turnover and transcription and can be applied to dissect gene expression programs in a wide range of organisms and conditions.

scholarly journals Codon choice directs constitutive mRNA levels in trypanosomes

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Janaina de Freitas Nascimento ◽  
Steven Kelly ◽  
Jack Sunter ◽  
Mark Carrington
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
Open Reading Frame ◽  
Mrna Turnover ◽  
Mrna Levels ◽  
Protein Coding ◽  
Reading Frame ◽  
Protein Coding Genes ◽  
The Relationship ◽  
Adaptation Index

Selective transcription of individual protein coding genes does not occur in trypanosomes and the cellular copy number of each mRNA must be determined post-transcriptionally. Here, we provide evidence that codon choice directs the levels of constitutively expressed mRNAs. First, a novel codon usage metric, the gene expression codon adaptation index (geCAI), was developed that maximised the relationship between codon choice and the measured abundance for a transcriptome. Second, geCAI predictions of mRNA levels were tested using differently coded GFP transgenes and were successful over a 25-fold range, similar to the variation in endogenous mRNAs. Third, translation was necessary for the accelerated mRNA turnover resulting from codon choice. Thus, in trypanosomes, the information determining the levels of most mRNAs resides in the open reading frame and translation is required to access this information.

Tristetraprolin: A cytosolic regulator of mRNA turnover moonlighting as transcriptional corepressor of gene expression

2021 ◽  
Author(s):  
Gabriel Rodríguez-Gómez ◽  
Alejandro Paredes-Villa ◽  
Mayte Guadalupe Cervantes-Badillo ◽  
Jessica Paola Gómez-Sonora ◽  
Jesús H. Jorge-Pérez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Turnover ◽  
Transcriptional Corepressor

Impact of high pH stress on yeast gene expression: A comprehensive analysis of mRNA turnover during stress responses

2015 ◽  
Vol 1849 (6) ◽  
pp. 653-664 ◽  
Author(s):  
David Canadell ◽  
José García-Martínez ◽  
Paula Alepuz ◽  
José E. Pérez-Ortín ◽  
Joaquín Ariño
Keyword(s):  
Gene Expression ◽  
Stress Responses ◽  
Comprehensive Analysis ◽  
Mrna Turnover ◽  
Yeast Gene ◽  
High Ph ◽  
Ph Stress

scholarly journals Global Analysis of Pub1p Targets Reveals a Coordinate Control of Gene Expression through Modulation of Binding and Stability

2005 ◽  
Vol 25 (13) ◽  
pp. 5499-5513 ◽  
Author(s):  
Radharani Duttagupta ◽  
Bin Tian ◽  
Carol J. Wilusz ◽  
Danny T. Khounh ◽  
Patricia Soteropoulos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Global Analysis ◽  
Affinity Purification ◽  
Mrna Turnover ◽  
Sequence Motifs ◽  
Posttranscriptional Control ◽  
Control Of Gene Expression ◽  
Transcript Stability ◽  
Distinct Sequence

ABSTRACT Regulation of mRNA turnover is an important cellular strategy for posttranscriptional control of gene expression, mediated by the interplay of cis-acting sequences and associated trans-acting factors. Pub1p, an ELAV-like yeast RNA-binding protein with homology to T-cell internal antigen 1 (TIA-1)/TIA-1-related protein (TIAR), is an important modulator of the decay of two known classes of mRNA. Our goal in this study was to determine the range of mRNAs whose stability is dependent on Pub1p, as well as to identify specific transcripts that directly bind to this protein. We have examined global mRNA turnover in isogenic PUB1 and pub1Δ strains through gene expression analysis and demonstrate that 573 genes exhibit a significant reduction in half-life in a pub1Δ strain. We also examine the binding specificity of Pub1p using affinity purification followed by microarray analysis to comprehensively distinguish between direct and indirect targets and find that Pub1p significantly binds to 368 cellular transcripts. Among the Pub1p-associated mRNAs, 53 transcripts encoding proteins involved in ribosomal biogenesis and cellular metabolism are selectively destabilized in the pub1Δ strain. In contrast, genes involved in transporter activity demonstrate association with Pub1p but display no measurable changes in transcript stability. Characterization of two candidate genes, SEC53 and RPS16B, demonstrate that both Pub1p-dependent regulation of stability and Pub1p binding require 3′ untranslated regions, which harbor distinct sequence motifs. These results suggest that Pub1p binds to discrete subsets of cellular transcripts and posttranscriptionally regulates their expression at multiple levels.

scholarly journals Cytoplasmic deadenylation: regulation of mRNA fate

2010 ◽  
Vol 38 (6) ◽  
pp. 1531-1536 ◽  
Author(s):  
Katrin Wiederhold ◽  
Lori A. Passmore
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Mrna Stability ◽  
Regulation Of Gene Expression ◽  
The Other ◽  
Mrna Turnover ◽  
Functional Roles ◽  
Specific Mrnas ◽  
Post Transcriptional Regulation ◽  
Mrna Fate

The poly(A) tail of mRNA has an important influence on the dynamics of gene expression. On one hand, it promotes enhanced mRNA stability to allow production of the protein, even after inactivation of transcription. On the other hand, shortening of the poly(A) tail (deadenylation) slows down translation of the mRNA, or prevents it entirely, by inducing mRNA decay. Thus deadenylation plays a crucial role in the post-transcriptional regulation of gene expression, deciding the fate of individual mRNAs. It acts both in basal mRNA turnover, as well as in temporally and spatially regulated translation and decay of specific mRNAs. In the present paper, we discuss mRNA deadenylation in eukaryotes, focusing on the main deadenylase, the Ccr4–Not complex, including its composition, regulation and functional roles.

Control of mRNA stability in eukaryotes

2006 ◽  
Vol 34 (1) ◽  
pp. 30-34 ◽  
Author(s):  
S.F. Newbury
Keyword(s):  
Gene Expression ◽  
Recent Work ◽  
Mrna Stability ◽  
Eukaryotic Cells ◽  
Mrna Turnover ◽  
Control Of Gene Expression

mRNA turnover plays a key role in the control of gene expression. Recent work has shown that proteins involved in mRNA turnover are located in multicomponent complexes which are tightly regulated. The control of mRNA stability is also intimately linked with translational processes. This article reviews the pathways and enzymes that control mRNA turnover in eukaryotic cells and discusses their mechanisms of control.

scholarly journals Expression of the c-myb and c-myc genes is regulated independently in differentiating mouse erythroleukemia cells by common processes of premature transcription arrest and increased mRNA turnover.

1988 ◽  
Vol 8 (9) ◽  
pp. 3938-3942 ◽  
Author(s):  
R J Watson
Keyword(s):  
Gene Expression ◽  
Erythroid Differentiation ◽  
Mrna Turnover ◽  
Mrna Levels ◽  
Rna Turnover ◽  
Control Of Gene Expression ◽  
Erythroleukemia Cells ◽  
Mouse Erythroleukemia

The mechanisms that modulate c-myb mRNA levels in mouse erythroleukemia cells induced toward erythroid differentiation were compared with those that act on c-myc. Both genes exhibited regulation at the levels of premature transcription arrest and RNA turnover. However, these common processes allowed temporally distinct control of gene expression.

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