Name: how cells control gene expression
Uploaded: 2020-11-23T11:47:37.000Z
Duration: 2 min 24 s
Channel: JoVE

Cells can precisely regulate gene expression at every step, from DNA to protein. This regulation occurs during transcription; during RNA processing, localization, and degradation; and during and after translation.&#160;
Transcriptional regulation is mediated by proteins that bind to regulatory sequences on DNA. These transcription factors are one of the most common ways to control gene expression and can either initiate transcription or prevent it.
Transcription generates pre mRNA that must be processed to mature mRNA through several regulated processes.&#160;
mRNA splicing, which removes the non-coding regions in precursor mRNA and joins the coding ones, controls gene expression through differential splicing patterns and RNA binding proteins.&#160; The addition of a poly-A tail and a 5&#8217; cap to produce the mature mRNA is also controlled.
Next, the mRNA must associate with RNA binding proteins to form a complex known as a ribonucleoparticle. This process is highly regulated, and only an mRNA that exists in a ribonucleoparticle can be transported from the nucleus to the cytoplasm to be translated.
Translational control is another crucial point for the regulation of gene expression. Regulation can be specific, where an individual or a subset mRNAs are involved, or general, where most mRNA transcripts are affected.&#160;
In specific regulation, inhibition of translation is controlled through interactions with trans-acting elements, such as proteins and certain types of RNA, including microRNAs and short interfering RNAs.
In general regulation, the various proteins involved in the translation machinery are activated or inhibited, which affects all transcripts.
Finally, post-translational modifications, such as phosphorylation, can either activate or deactivate proteins, while others, like ubiquitination, can lead to their degradation.

regulatie van expressie vindt plaats in meerdere stappen

Regulation of Expression Occurs at Multiple Steps

Genexpressie kan bij vrijwel elke stap, van gen tot eiwit, worden gereguleerd. Transcriptie is de stap die het meest wordt gereguleerd. Dit omvat de binding van eiwitten aan korte regulerende sequenties op het DNA. Deze associatie kan de transcriptie van een gen geassocieerd met de respectieve sequentie bevorderen of remmen.

Transcriptie resulteert in het genereren van een precursor (pre-mRNA) die uit zowel exons als introns bestaat, die verdere verwerking nodig heeft voordat deze naar een eiwit wordt transleerd. Dit gebeurt door middel van mRNA-splitsing, waarbij niet-coderende gebieden worden verwijderd en de coderende gebieden worden samengevoegd. mRNA-verwerking kan ook worden gebruikt als een regulerend mechanisme door variatie in splitsingspatronen, zoals het overslaan van bepaalde exons, alternatieve splitsing en het opnemen van introns.

De toevoeging van een poly-A-staart aan het 3’-uiteinde en een 5’-kap om het volwassen mRNA te produceren zijn ook regulerende punten tijdens de RNA-verwerking. Regulatie vindt plaats door variatie in het polyadenylatiesignaal, dat bepaalt waar de poly-A-staart aan het mRNA wordt toegevoegd. In sommige gevallen is er meer dan één poly-A-signaal aanwezig aan het 3’-uiteinde, wat de lengte van het 3’-niet-getranslateerde gebied zal veranderen, maar het uiteindelijke eiwitproduct zal hetzelfde zijn. De stabiliteit en het translatiepotentieel van de mRNA-varianten kunnen echter verschillen, wat de geproduceerde hoeveelheid eiwit kan veranderen. In andere gevallen is er een extra poly-A-signaal aanwezig op het intron of exon binnen de gensequentie, wat kan leiden tot variatie in splitsingsplaatsen voor polyadenylatie en kan resulteren in verschillende eiwitten uit dezelfde pre-mRNA-streng. De toevoeging van de 5 'cap, dat bestaat uit gemethyleerde guanosine, wordt gereguleerd door twee mechanismen. Eén betreft de regulatie van de methyltransferasen die de methylgroep aan de guanosine toevoegen, en de andere is via regulatie van de cellulaire signaalroutes die tot methylering leiden.

Vervolgens moet het volwassen mRNA via nucleaire poriecomplexen (NPC's) van de kern naar het cytoplasma worden getransporteerd om te worden transleerd. Dit wordt gereguleerd door het mRNA en vormt een complex, bekend als het ribonucleodeeltje, met RNA-bindende eiwitten. NPC's laten alleen mRNA's die zich in het complex bevinden, in het cytoplasma terecht. Zodra een mRNA het cytoplasma binnenkomt voor translatie, kan het individueel of als onderdeel van een groep worden getarget via specifieke regelgeving, of het kan een gemeenschappelijke regulatie ondergaan met alle andere mRNA's in het cytoplasma. Bij specifieke regulatie reguleren bepaalde transwerkende elementen, zoals eiwitten en verschillende soorten RNA's, de transcriptie. Bij algemene regulatie worden de eiwitten die betrokken zijn bij de translatiemechanismes geactiveerd of geremd, wat op zijn beurt de translatie van alle transcripten beïnvloedt. Het meest voorkomende translationele regulerende mechanisme is de wijziging van de translatie-initiatiefactor.

Genexpressie kan ook worden gereguleerd door middel van post-translationele modificaties, waarbij een door enzym gekatalyseerde omkeerbare modificatie de functie van een eiwit kan veranderen. Een veel voorkomende post-translationele modificatie is fosforylering, die wordt uitgevoerd door enzymen die bekend staan als kinasen. Defosforylering van eiwitten wordt daarentegen uitgevoerd door eiwitten die bekend staan ​​als fosfatasen. Fosforylering van een eiwit kan resulteren in de activering of deactivering ervan en de functie ervan veranderen.

Regulatie van expressie vindt plaats in meerdere stappen

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 ...

regulation-of-expression-occurs-at-multiple-steps

Education

JoVE Core

Molecular Biology

Moleculaire biologie

Unit 1

Gene Expression

Genexpressie

KEY TERMS AND CONCEPTS

BELANGRIJKE TERMEN EN CONCEPTEN

how cells control gene expression

Cells control gene expression at several points between DNA and protein. The most common control point is transcription. At this stage, proteins bind to short regulatory DNA sequences and can either increase or reduce transcription of the linked gene.

After transcription, a precursor mRNA is made. This pre-mRNA contains exons, which code for protein, and introns, which do not. It must be processed before translation, and splicing removes the introns and joins the exons. Cells can also regulate gene expression through changes in splicing patterns, including skipping certain exons, alternative splicing, and including introns.

RNA processing also includes adding a 3' poly-A tail and a 5' cap to form mature mRNA. The poly-A tail is added at a site marked by a polyadenylation signal. In some cases, more than one poly-A signal is present at the 3' end. This can change the length of the 3' untranslated region without changing the final protein, but the mRNA variants may differ in stability and translation potential. In other cases, an extra poly-A signal in an intron or exon can change splicing during polyadenylation and produce different proteins from the same pre-mRNA strand.

The 5' cap is a methylated guanosine, and its addition is also regulated. One control route acts through methyltransferases, the enzymes that add the methyl group. Another route works through cellular signaling pathways that lead to methylation. After processing, mature mRNA must leave the nucleus through nuclear pore complexes. It does this by forming a ribonucleoparticle with RNA-binding proteins, and only mRNAs in this complex can pass into the cytoplasm.

Once mRNA reaches the cytoplasm, translation can be regulated in specific ways or in a more general way. Specific regulation affects particular transcripts through trans-acting elements such as proteins and different types of RNA. General regulation affects all cytoplasmic mRNAs by turning translation machinery proteins on or off. The most common translational control step is modification of the translation initiation factor. Gene expression can also change after a protein is made through post-translational modifications. A common example is phosphorylation, which is carried out by kinases, while phosphatases remove the phosphate group through dephosphorylation. Phosphorylation can activate or deactivate a protein and change its function.

How Cells Control Gene Expression

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regulation of expression occurs at multiple steps

Cells control gene expression at several points between DNA and protein. The most common control point is transcription. At this stage, proteins bind to short regulatory DNA sequences and can either increase or reduce transcription of the linked gene. After transcription, a precursor mRNA is made. This pre-mRNA contains exons, which code for protein, and introns, which do not. It must be processed before translation, and splicing removes the introns and joins the exons. Cells can also regulate...

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The eukaryotic promoter region is a stretch of DNA located upstream of a gene. It includes an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. These DNA signals help control when transcription begins. The promoter can be divided into proximal and distal regions. The proximal promoter lies close to the gene and includes cis-regulatory sequences and the core promoter. The core promoter is the RNA polymerase binding site, and it is usually found...

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Transcription activators are proteins that help turn genes on by promoting transcription from DNA to RNA. They often have two parts. One part binds to DNA, and the other part activates transcription. In some proteins, such as the glucocorticoid receptor and MyoD, one domain can do both jobs. The DNA-binding part recognizes specific regulatory sequences on the DNA. These binding domains are grouped into families based on their structure. Common examples include the leucine zipper, zinc finger,...

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epigenetic regulation

DNA Methylation and Histone Changes

Epigenetic regulation controls gene activity without changing the DNA sequence. It helps determine when genes are turned on or off in a cell. Two major epigenetic mechanisms are DNA methylation and histone modification. DNA methylation adds chemical groups to DNA, while histone changes affect how tightly DNA is packed around histone proteins. These changes can make genes easier or harder to use. In high school biology, epigenetic regulation is important for understanding how cells with the...

genomic imprinting and inheritance

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Genomic imprinting affects how some inherited genes are turned on or off in human cells. Diploid organisms inherit chromosomes from both parents, and each gene usually has two alleles. In most cases, both alleles are expressed. If one allele is missing or mutated, the other can often compensate, but some genes do not work that way. In genomic imprinting, a gene or its regulatory sequence carries chemical tags, such as methyl groups, on the copy inherited from only one parent. These tags are...

key terms and concepts

Explore how gene expression is controlled at transcription, RNA processing, mRNA export, translation, and protein phosphorylation in high school biology.

How Cells Control Gene Expression | JoVE K12

molecular biology

JoVE Core Molecular Biology showcases the molecular processes of the cell through clear and concise animated video lessons. Additionally, in scientist-in-action videos, these concepts' application is demonstrated through real experiments in modern laboratories.

How Cells Control Gene Expression

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