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

细胞可以精确调节 基因表达的每一步，从DNA到蛋白质。发生此规定 在转录过程中 在RNA加工过程中 本地化和退化 以及在和 翻译后。转录的 调节是中介的 通过与之结合的蛋白质 DNA上的调控序列。这些转录因子 是最常见的方式之一 控制基因 表达，并且可以 开始转录 或防止它。转录 产生前mRNA，必须加工成熟 mRNA通过几种调控 流程。mRNA剪接，去除了 前体中的非编码区 mRNA并加入编码 一个，控制基因表达 通过差分拼接 模式和RNA结合 蛋白质。聚（A）的添加 尾巴和5端帽 产生成熟 mRNA也受到控制。接下来，mRNA必须缔合 与RNA结合蛋白 形成一个复杂的已知 作为核糖核颗粒。这个过程是 受到严格监管 只有一个存在的mRNA 在核糖核酸颗粒中 可以运输 从细胞核 到细胞质 待翻译。平移控制 是另一个关键点 进行监管 基因表达 监管可以是 具体的，到 个体或子集 的mRNA被涉及 或是大体的，其中大多数mRNA 转录本受到影响。在具体规定中，抑制翻译 被控制 通过互动 具有这样的交易元素 作为蛋白质和某些类型 的RNA，包括microRNA 和短干扰RNA。在一般规定中，各种蛋白质 参与 翻译机械 被激活或禁止 这会影响所有转录本。最后，翻译后 修改 如磷酸化可以 激活或停用 蛋白质而其它 像泛素化 会导致它们退化。

<ol>
	<li>Alberts 等人，第 6 版;第 372 页</li>
	<li>Lodish H， Berk A， Zipursky SL， et al. 分子细胞生物学。第 4 版。纽约:W. H. Freeman;2000. 第 11.3 节，mRNA 加工的调节。</li>
	<li>瓦伦西亚-桑切斯，MA，刘，J.，汉农，GJ，和帕克，R.（2006）。控制 miRNA 和 siRNA 的翻译和 mRNA 降解。基因与发展，20（5），515-524。</li>
	<li>Lei， E. P.， & Silver， P. A. （2002年）。蛋白质和 RNA 从细胞核输出。发育细胞，2（3），261-272。</li>
	<li>Hershey， John W B et al. "转化控制原则:概述"。冷泉港生物学观点，第 4,12 卷，a011528。2012 年 12 月 1 日，doi:10.1101/cshperspect.a011528</li>
</ol>

表达调控发生在多个步骤

Regulation of Expression Occurs at Multiple Steps

从基因到蛋白的几乎每个步骤都可以调控基因表达。 转录是最常受到调控的步骤。 这涉及蛋白与 DNA 上短调控序列的结合。 这种关联可以促进或抑制与相应序列相关的基因的转录。

转录会产生由外显子和内含子组成的前体（前 mRNA），在翻译成蛋白之前需要进一步加工。 这是通过 mRNA 剪接发生的，其中涉及非编码区域的去除和编码区域的合并。 mRNA 加工还可以通过剪接模式的变化（例如跳过某些外显子、选择性剪接和包含内含子）用作调控机制。

在 3' 端添加多聚 A 尾和 5' 帽以产生成熟的 mRNA 也是 RNA 加工过程中的调节点。 调节是通过聚腺苷酸化信号的变化而发生的，这决定了聚腺苷酸尾将添加到 mRNA 上的位置。 在某些情况下，3'端存在多个多聚腺苷酸信号，这将改变3'非翻译区的长度，但最终的蛋白产物将是相同的。 然而，变体 mRNA 的稳定性和翻译潜力可能不同，这可能会改变产生的蛋白的量。 在其他情况下，基因序列内的内含子或外显子上存在额外的多聚腺苷酸信号，这可能导致多聚腺苷酸化的剪接位点发生变化，并导致来自前体 mRNA 的同一链产生不同的蛋白。添加 5 个 由甲基化鸟苷组成的帽由两种机制调节。 一种涉及将甲基添加到鸟苷上的甲基转移酶的调节，另一种是通过调节导致甲基化的细胞信号传导途径。

接下来，成熟的 mRNA 需要通过核孔复合物 (NPC) 从细胞核转运到细胞质进行翻译。 这受到 mRNA 的调节，与 RNA 结合蛋白形成复合物，称为核糖核颗粒。 NPC 只允许复合物中的 mRNA 进入细胞质。 一旦 mRNA 进入细胞质进行翻译，它可以通过特定的调节单独或作为一组的一部分被靶向，或者它可以与细胞质中的所有其他 mRNA 一起经历共同的调节。 在具体调控中，特定的反式作用元件（如蛋白和不同类型的 RNA）调控转录。 在一般调节中，参与翻译机制的蛋白被激活或抑制，进而影响所有转录本的翻译。 最常见的翻译调控机制是翻译起始因子的修饰。

基因表达也可以通过翻译后修饰来调节，其中酶催化的可逆修饰可以改变蛋白的功能。 一种常见的翻译后修饰是磷酸化，它是由称为激酶的酶进行的。 另一方面，蛋白的去磷酸化是由称为磷酸酶的蛋白进行的。 蛋白的磷酸化可导致其激活或失活并改变其功能。

基因表达在从基因到蛋白质的几乎每一个步骤中都可能受到调控。其中，转录是最常被调控的步骤。这一过程涉及……

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

Education

教育

JoVE Core

Molecular Biology

分子生物学

Unit 1

第一单元

Gene Expression

基因表达

KEY TERMS AND CONCEPTS

关键术语与概念

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 分子生物学通过清晰简洁的动画视频课程展示了细胞的分子过程。此外，在科学家在行动的视频中，这些概念的应用是通过现代实验室中的真实实验演示的。

How Cells Control Gene Expression

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