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Related Concept Videos

Regulation of Expression at Multiple Steps01:23

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 addition of a...
Translational Regulation01:29

Translational Regulation

Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
What is Gene Expression?01:36

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 processed and...
What is Gene Expression?01:42

What is Gene Expression?

Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
Regulation of Expression Occurs at Multiple Steps02:24

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 Steps02:24

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...

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Deciphering the rules by which 5'-UTR sequences affect protein expression in yeast.

Shlomi Dvir1, Lars Velten, Eilon Sharon

  • 1Departments of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.

Proceedings of the National Academy of Sciences of the United States of America
|July 9, 2013
PubMed
Summary

Altering short sequences in the 5' untranslated region (5'-UTR) of messenger RNAs (mRNAs) significantly impacts protein levels. Computational models accurately predict these expression changes, aiding in predictable protein production control.

Keywords:
AUG sequence contextcomputational predictionmRNA foldingpost-transcriptional regulationupstream start codons

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Saccharomyces cerevisiae Metabolic Labeling with 4-thiouracil and the Quantification of Newly Synthesized mRNA As a Proxy for RNA Polymerase II Activity

Published on: October 22, 2018

Area of Science:

  • Molecular Biology
  • Genetics
  • Systems Biology

Background:

  • The 5'-untranslated region (5'-UTR) of messenger RNAs (mRNAs) influences gene expression, but the underlying sequence-based rules are not fully understood.
  • Understanding 5'-UTR sequence effects is crucial for controlling protein synthesis and cellular function.

Purpose of the Study:

  • To investigate the impact of specific 5'-UTR sequences on protein production levels in yeast.
  • To develop predictive computational models for protein expression based on 5'-UTR sequence variations.

Main Methods:

  • Construction of a large-scale yeast mutant library with variations in the 10 base pairs preceding the start codon of a fluorescent reporter.
  • High-throughput sequencing to accurately quantify protein abundance for over 2,000 unique 5'-UTR sequence variants.
  • Development and validation of computational models to predict protein expression variability.

Main Results:

  • Significant variation (approximately sevenfold range) in protein levels was observed due to minor sequence changes in the 5'-UTR.
  • Computational models successfully predicted over 70% of the expression variability in independent datasets.
  • Key sequence features influencing protein abundance include start codon context, mRNA secondary structure, and upstream AUGs (uAUGs).

Conclusions:

  • 5'-UTR sequences, particularly near the start codon, play a dominant role in modulating protein expression levels.
  • The developed models provide a framework for predictably tuning protein expression through 5'-UTR sequence manipulation.
  • This research advances the understanding of gene expression regulation at the translational level.