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

細胞はDNAからタンパク質まで、あらゆる段階で遺伝子発現を正確に調節することができます。この調節は転写中に発生します。RNAのプロセシング、局在化、および分解中。そして翻訳中と翻訳後。 
転写調節は、DNA上の調節配列に結合するタンパク質によって媒介されます。これらの転写因子は、遺伝子発現を制御する最も一般的な方法の1つであり、転写を開始または防止することができます。
転写は、いくつかの制御されたプロセスを通じて成熟したmRNAに処理しなければならないプレmRNAを生成します。 
mRNAスプライシングは、前駆体mRNAの非コード領域を除去し、コード領域を結合し、差動スプライシングパターンとRNA結合タンパク質を通じて遺伝子発現を制御します。成熟したmRNAを生成するためのpoly-Aテールと5'キャップの添加も制御されます。
次に、mRNAはRNA結合タンパク質と結合して、リボ核粒子として知られる複合体を形成する必要があります。このプロセスは高度に制御されており、リボ核粒子に存在するmRNAのみが核から細胞質に輸送されて翻訳されます。
翻訳制御は、遺伝子発現の調節のためのもう一つの重要なポイントです。調節は、個々のmRNAまたはサブセットのmRNAが関与する特定のものもあれば、ほとんどのmRNA転写産物が影響を受ける一般的なものも含みます。 
特定の制御では、翻訳の阻害は、タンパク質やマイクロRNAや短い干渉RNAを含む特定の種類のRNAなどのトランス作用要素との相互作用によって制御されます。
一般的な調節では、翻訳機構に関与するさまざまなタンパク質が活性化または阻害され、それがすべての転写産物に影響を与えます。
最後に、リン酸化などの翻訳後修飾はタンパク質を活性化または不活性化することができますが、ユビキチン化などの他のものはタンパク質の分解につながる可能性があります。

<ol>
	<li>Alberts et al., 6th edition; page 372 (英語</li>)
	<li>Lodish H、Berk A、Zipursky SL、et al. 分子細胞生物学。ニューヨーク:WHフリーマン;2000. セクション 11.3、mRNA プロセシングの規制。</li>
	<li>バレンシア・サンチェス、MA、劉、J.、ハノン、GJ、およびパーカー、R.(2006)。miRNAおよびsiRNAによる翻訳およびmRNA分解の制御。遺伝子と発達, 20(5), 515-524.</li>
	<li>Lei, E. P., & Silver, P. A. (2002).核からのタンパク質とRNAの輸送。発生細胞, 2(3), 261-272.</li>
	<li>Hershey, John W B et al. "Principles of translational control: an overview." Cold Spring Harbor perspectives in biology, vol. 4,12, a011528. 2012年12月1日, doi:10.1101/cshperspect.a011528</li>
</ol>

表現の制御は複数の段階で発生する

Regulation of Expression Occurs at Multiple Steps

遺伝子発現は、遺伝子からタンパク質に至るほぼすべての段階で制御できます。転写は、最も一般的に規制されるステップです。これには、DNA上の短い調節配列へのタンパク質の結合が含まれます。 この関連性は、それぞれの配列に関連する遺伝子の転写を促進または阻害することができます。

転写により、エクソンとイントロンの両方からなる前駆体(pre-mRNA)が生成されますが、これはタンパク質に翻訳される前にさらなる処理が必要です。これは、非コード領域の除去とコード領域の結合を含むmRNAスプライシングによって起こります。mRNAプロセシングは、特定のエクソンのスキッピング、選択的スプライシング、イントロンの組み込みなどのスプライシング パターンの変化を介した制御機構としても使用できます。

成熟mRNAを生成するための3’末端のポリAテールと5’キャップの付加も、RNAプロセシング中の制御ポイントです。調節は、ポリアデニル化シグナルの変化を通じて起こり、ポリAテールがmRNA上のどこに追加されるかを決定します。場合によっては、3’末端に複数のポリAシグナルが存在し、3’非翻訳領域の長さが変化しますが、最終的なタンパク質産物は同じになります。ただし、変異体mRNAの安定性と翻訳能力は異なる可能性があり、生成されるタンパク質の量が変化する可能性があります。他の場合には、追加のポリAシグナルが遺伝子配列内のイントロンまたはエクソンに存在し、ポリアデニル化のスプライシング部位の変動を引き起こし、pre-mRNAの同じ鎖から異なるタンパク質が生成される可能性があります。 ' キャップはメチル化グアノシンで構成されており、2つのメカニズムによって制御されています。1つはグアノシンにメチル基を付加するメチルトランスフェラーゼの制御に関係し、もう1つはメチル化を引き起こす細胞シグナル伝達経路の制御によるものです。

次に、成熟mRNA は、核膜孔複合体(NPC)を介して核から細胞質に輸送され、翻訳される必要があります。 これは、mRNAによって制御され、RNA結合タンパク質とリボ核粒子として知られる複合体を形成します。NPC は、複合体内にあるmRNAのみが細胞質に入ることができます。mRNAが翻訳のために細胞質に入ると、特定の制御によって個別にまたはグループの一部として標的化されるか、細胞質内の他のすべてのmRNAと共通の制御を受けることができます。特定の制御では、タンパク質やさまざまな種類のRNAなどの特定のトランス作用要素が転写を制御します。一般的な制御では、翻訳機構に関与するタンパク質が活性化または阻害され、それがすべての転写物の翻訳に影響を与えます。 最も一般的な翻訳調節機構は、翻訳開始因子の修飾です。

遺伝子発現は翻訳後修飾によっても調節でき、酵素触媒による可逆的修飾によってタンパク質の機能が変化します。一般的な翻訳後修飾はリン酸化であり、これはキナーゼとして知られる酵素によって行われます。一方、タンパク質の脱リン酸化は、ホスファターゼとして知られるタンパク質によって行われます。タンパク質のリン酸化により、その活性化または不活性化が生じ、その機能が変化することがあります。

遺伝子発現は、遺伝子からタンパク質までのほぼすべてのステップで制御することができます。トランスクリプションは、最も一般的に規制されているステップです。これには、...

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

Education

JoVE Core

Molecular Biology

分子生物学

Unit 1

ユニット1

Gene Expression

遺伝子発現

KEY TERMS AND CONCEPTS

主要用語と概念

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 分子生物学は、明確で簡潔なアニメーション ビデオ レッスンを通じて細胞の分子プロセスを紹介します。さらに、科学者の実際のビデオでは、これらの概念の応用が現代の研究室での実際の実験を通じて実証されています。

How Cells Control Gene Expression

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