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Regulation of Expression at Multiple Steps

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...

Regulation of Expression Occurs at Multiple Steps

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...

Regulation of Expression Occurs at Multiple Steps

Regulation of Expression Occurs at Multiple Steps

mRNA Stability and Gene Expression

mRNA Stability and Gene Expression

The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability

mRNA Stability and Gene Expression

mRNA Stability and Gene Expression

What is Gene Expression?

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...

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High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes

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Multiplexed gene control reveals rapid mRNA turnover.

Antoine Baudrimont¹, Sylvia Voegeli¹, Eduardo Calero Viloria¹

¹Biozentrum, University of Basel, 4056 Basel, Switzerland.

Science Advances

|July 15, 2017

Summary

Researchers developed a new method to measure mRNA synthesis and decay rates, revealing faster mRNA turnover than previously thought. This finding impacts understanding of gene expression and network behavior.

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Area of Science:

Molecular Biology
Systems Biology
Genetics

Background:

mRNA expression levels are determined by synthesis and decay rates, which are tightly controlled.
Measuring these rates is challenging due to coordinated control, leading to low correlation among existing methods.
Accurate measurement of mRNA half-lives is crucial for understanding gene regulation.

Purpose of the Study:

To develop a minimally invasive method for measuring mRNA synthesis and decay rates.
To validate the new method by comparing results with established techniques.
To investigate the impact of rapid mRNA turnover on gene expression dynamics.

Main Methods:

Developed a multiplexed gene control method to shut off gene expression using synthetic promoters.
Validated the method by measuring nascent to mature mRNA ratios and half-lives with controllable endogenous promoters.
Compared results with the metabolic pulse-labeling method in yeast.

Main Results:

The new method showed high correlation with the metabolic pulse-labeling method for yeast mRNA half-lives.
Observed significantly faster mRNA degradation than previously estimated, with a median half-life of approximately 2 minutes.
Determined promoter-dependent and promoter-independent transcription rates, with the latter showing a broader dynamic range than half-lives.

Conclusions:

The developed multiplexed gene control method accurately measures mRNA half-lives and transcription rates.
Rapid mRNA turnover and adjustable transcription rates significantly influence stochastic gene expression and network behavior.
This method provides a valuable tool for dissecting gene expression dynamics and regulatory mechanisms.