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

Las células pueden regular con precisión la expresión génica en cada paso, desde el ADN hasta la proteína. Esta regulación se produce durante la transcripción; durante el procesamiento, localización y degradación del ARN; y durante y después de la traducción. 
La regulación transcripcional está mediada por proteínas que se unen a secuencias reguladoras en el ADN. Estos factores de transcripción son una de las formas más comunes de controlar la expresión génica y pueden iniciar la transcripción o prevenirla.
La transcripción genera pre ARNm que debe ser procesado para madurar el ARNm a través de varios procesos regulados. 
empalme de ARNm, que elimina las regiones no codificantes en el ARNm precursor y se une a las codificantes, controla la expresión génica a través de patrones de empalme diferenciales y proteínas de unión al ARN. También se controla la adición de una cola de poli-A y una tapa de 5' para producir el ARNm maduro.
A continuación, el ARNm debe asociarse con proteínas de unión al ARN para formar un complejo conocido como ribonucleoparticle. Este proceso está altamente regulado, y solo un ARNm que existe en una ribonucleoppartícula puede ser transportado desde el núcleo hasta el citoplasma para ser traducido.
El control traslacional es otro punto crucial para la regulación de la expresión génica. La regulación puede ser específica, cuando están implicados un individuo o un subconjunto de ARNm, o general, cuando se ven afectados la mayoría de los transcritos de ARNm. 
En la regulación específica, la inhibición de la traducción se controla a través de interacciones con elementos que actúan trans, como proteínas y ciertos tipos de ARN, incluidos los microARN y los ARN interferentes cortos.
En la regulación general, las diversas proteínas involucradas en la maquinaria de traducción se activan o inhiben, lo que afecta a todas las transcripciones.
Finalmente, las modificaciones postraduccionales, como la fosforilación, pueden activar o desactivar proteínas, mientras que otras, como la ubiquitinación, pueden conducir a su degradación.

<ol>
	<li>Alberts et al., 6ª edición; página 372</li>
	<li>Lodish H, Berk A, Zipursky SL, et al. Biología celular molecular. 4ª edición. Nueva York: W. H. Freeman; 2000. Sección 11.3, Regulación del procesamiento de ARNm.</li>
	<li>Valencia-Sánchez, M. A., Liu, J., Hannon, G. J., & Parker, R. (2006). Control de la traducción y degradación del ARNm por miRNAs y siRNAs. Genes y desarrollo, 20(5), 515-524.</li>
	<li>Lei, E. P., y Silver, P. A. (2002). Exportación de proteínas y ARN desde el núcleo. Célula de desarrollo, 2(3), 261-272.</li>
	<li>Hershey, John W B et al. "Principios de control traslacional: una visión general". Perspectivas de Cold Spring Harbor en biología vol. 4,12 a011528. 1 de diciembre de 2012, doi:10.1101/cshperspect.a011528</li>
</ol>

la regulación de la expresión ocurre en múltiples pasos

Regulation of Expression Occurs at Multiple Steps

La expresión genética se puede regular en casi todos los pasos, desde el gen hasta la proteína. La transcripción es el paso que más comúnmente se regula. Esto implica la unión de proteínas a secuencias reguladoras cortas del ADN. Esta asociación puede promover o inhibir la transcripción de un gen asociado con la secuencia respectiva.

La transcripción da como resultado la generación de un precursor (pre-ARNm) que consta de exones e intrones, que necesita un procesamiento adicional antes de traducirse a una proteína. Esto sucede mediante el empalme del ARNm, que implica la eliminación de regiones no codificantes y la fusión de las codificantes. El procesamiento de ARNm también se puede utilizar como mecanismo regulador mediante la variación en los patrones de empalme, como la omisión de ciertos exones, el empalme alternativo y la inclusión de intrones.

La adición de una cola poli-A en el extremo 3' y una tapa 5' para producir el ARNm maduro también son puntos reguladores durante el procesamiento del ARN. La regulación se produce mediante la variación en la señal de poliadenilación, que determina dónde se agregará la cola poli-A al ARNm. En algunos casos, hay más de una señal poli-A presente en el extremo 3', lo que cambiará la longitud de la región no traducida 3', pero el producto proteico final será el mismo. Sin embargo, la estabilidad y el potencial de traducción de las variantes de ARNm pueden diferir, lo que puede alterar la cantidad de proteína producida. En otros casos, una señal poli-A adicional está presente en el intrón o exón dentro de la secuencia del gen, lo que puede conducir a una variación en los sitios de empalme para la poliadenilación y dar lugar a diferentes proteínas de la misma cadena de pre-ARNm. ' cap, que se compone de guanosina metilada, está regulada por dos mecanismos. Uno implica la regulación de las metiltransferasas que añaden el grupo metilo a la guanosina, y el otro es mediante la regulación de las vías de señalización celular que conducen a la metilación.

A continuación, el ARNm maduro debe transportarse desde el núcleo al citoplasma a través de complejos de poros nucleares (NPC) para ser traducido. Esto está regulado por el ARNm para formar un complejo, conocido como ribonucleopartícula, con las proteínas de unión al ARN. Los NPC solo permiten que los ARNm que están en el complejo pasen al citoplasma. Una vez que un ARNm ingresa al citoplasma para su traducción, puede seleccionarse individualmente o como parte de un grupo mediante regulaciones específicas, o puede someterse a una regulación común con todos los demás ARNm del citoplasma. En la regulación específica, determinados elementos que actúan en trans, como proteínas y diferentes tipos de ARN, regulan la transcripción. En la regulación general, las proteínas implicadas en la maquinaria de traducción se activan o inhiben, lo que a su vez afecta a la traducción de todos los transcritos. El mecanismo regulador de la traducción más común es la modificación del factor de iniciación de la traducción.

La expresión génica también se puede regular mediante modificaciones postraduccionales, donde una modificación reversible catalizada por una enzima puede alterar la función de una proteína. Una modificación postraduccional común es la fosforilación, que se lleva a cabo mediante enzimas conocidas como quinasas. La desfosforilación de proteínas, por otro lado, la llevan a cabo proteínas conocidas como fosfatasas. La fosforilación de una proteína puede provocar su activación o desactivación y alterar su función.

La regulación de la expresión ocurre en múltiples pasos

La expresión génica se puede regular en casi todos los pasos, desde el gen hasta la proteína. La transcripción es el paso más comúnmente regulado. Esto implica el ...

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

Education

Educación

JoVE Core

Molecular Biology

Biología Molecular

Unit 1

Unidad 1

Gene Expression

Expresión génica

KEY TERMS AND CONCEPTS

TÉRMINOS Y CONCEPTOS CLAVE

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

cell specific gene expression

How Cells Switch Genes On and Off

Cells switch genes on and off to make different proteins for different jobs. In multicellular organisms, many cell types are built from the same DNA, but they do not use the same genes in the same way. This difference in gene expression helps explain why cells can look and act so differently. Liver cells are a clear example. They help detoxify blood, make bile to help digest fats, and produce proteins needed for metabolism. To do these jobs, liver cells must express a specific set of genes.

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...

cis-regulatory sequences

How Cis-Regulatory DNA Controls Transcription

Cis-regulatory sequences are short, non-coding DNA segments that control gene transcription. They sit on the same chromosome as the genes they regulate and act as binding sites for transcriptional regulators. In eukaryotes, these proteins help control gene expression patterns in different cell types. These DNA sequences can be close to a gene or thousands of bases away. When they are far from the gene in the DNA sequence, they are often brought close together in space because chromosomes are...

cooperative binding of transcription regulators

cooperative-binding-of-transcription-regulators

How Transcription Factors Bind DNA

Transcriptional regulators bind to cis-regulatory DNA sequences to control gene transcription. These DNA sequences are very short, usually fewer than ten nucleotide pairs long. Because they are so short, the same sequence can appear by chance in many places across the genome. Some regulators can also bind to groups of similar sequences. That raises the chance of random binding even more. To lower this risk, transcription regulators often form dimers, which are pairs of proteins that bind a DNA...

prokaryotic transcriptional activators and repressors

prokaryotic-transcriptional-activators-and-repressors

Operon Control by Activators and Repressors

Operon control in prokaryotes depends on activators and repressors. Prokaryotic genes are often arranged in groups, not one by one like in eukaryotes. Genes that help carry out the same biochemical process are placed together with their regulatory elements. This group is called an operon, and it is transcribed into a single polycistronic mRNA strand. Activators and repressors are DNA-binding proteins that control transcription in an operon. Activators bind near the promoter, which is the site...

operons

Operons in Bacterial Gene Control

Operons help bacteria control groups of genes at the same time. An operon is a set of genes that are regulated together and can be turned on or off as a unit. This shared control helps bacteria respond quickly to changes in their environment. In many operons, a promoter gives RNA polymerase a place to bind and start transcription. The operon also includes a regulatory region that helps control whether the genes are expressed. When conditions change, the cell can use this setup to manage gene...

the eukaryotic promoter region

Eukaryotic Promoter Motifs and Gene Control

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...

co-activators and co-repressors

Chromatin Control in Gene Transcription

Chromatin control plays a major role in gene transcription in eukaryotes. Gene expression is regulated by several proteins that work together at a gene regulatory site. Some of these proteins bind directly to specific DNA sequences, while co-regulators attach to those regulators but do not bind DNA on their own. Co-regulators can act as co-activators or co-repressors, depending on the complex they join. One co-regulator may even switch roles in different settings. For example, the...

eukaryotic transcription activators

How Transcription Activators Turn Genes On

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,...

eukaryotic transcription inhibitors

How Eukaryotic Gene Repressors Work

Eukaryotic gene repressors help turn specific genes off when the cell needs to control growth, development, or other biochemical processes. These DNA-binding proteins regulate gene expression in eukaryotes. Their presence at the right time and place can be triggered by hormones and signals from other cells. Most transcription inhibitors have two main parts. One part binds DNA, and the other is a repressor domain, which helps shut down transcription. Repressor domains can connect with basal...

combinatorial gene control

Gene Expression by Transcription Factor Combinations

Gene expression can depend on combinations of transcription factors working together. In combinatorial gene control, several transcription factors act in a coordinated way to regulate a single gene. If one or more of these factors are missing, the level of gene expression or repression can change a lot. This kind of control helps explain how a relatively small number of transcription factors can regulate a very large number of genes. More than 30,000 genes are controlled by about 2,000 to...

induced pluripotent stem cells

Reprogramming Cells into Stem Cells

Induced pluripotent stem cells are created by reprogramming mature cells back into a stem-cell state. This process shows that specialized cells can be changed into cells with broader developmental potential. The topic is important in biology because it links cell identity, gene control, and stem cell research. These cells begin as ordinary body cells and are pushed to de-differentiate, or lose their specialized features. After reprogramming, they behave like pluripotent stem cells, which means...

master transcription regulators

MEF2C and Gene Control Cascades

MEF2C is a master transcription regulator that controls gene expression in coordinated cascades. These regulators are proteins that manage the activity of multiple genes that often work together to produce a complex outcome. When a master transcription regulator is activated, it can start a chain of transcriptional activation that supports that outcome. Master transcription regulators can act in two main ways. They may bind directly to the regulatory sequences of several genes involved in a...

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

Genomic Imprinting in Human Disease

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 Biología Molecular presenta los procesos moleculares de la célula a través de lecciones claras y concisas de animaciones audiovisuales. Además, en los vídeos de científicos en acción, se muestran aplicaciones de estos conceptos mediante experimentos reales en laboratorios especializados.

How Cells Control Gene Expression

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