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

세포는 DNA에서 단백질에 이르기까지 모든 단계에서 유전자 발현을 정확하게 조절할 수 있습니다. 이 규정은 전사 중에 발생합니다. RNA 처리, 국소화 및 분해 중; 그리고 번역 중과 번역 후. 
전사 조절은 DNA의 조절 서열에 결합하는 단백질에 의해 매개됩니다. 이러한 전사 인자는 유전자 발현을 제어하는 가장 일반적인 방법 중 하나이며 전사를 시작하거나 방지할 수 있습니다.
전사는 여러 조절된 과정을 통해 mRNA를 성숙시키기 위해 처리해야 하는 사전 mRNA를 생성합니다. 
mRNA 스플라이싱은 전구체 mRNA의 비코딩 영역을 제거하고 코딩 영역을 결합하며, 차등 스플라이싱 패턴과 RNA 결합 단백질을 통해 유전자 발현을 제어합니다.성숙한 mRNA를 생성하기 위해 poly-A 꼬리와 5' 캡을 추가하는 것도 제어됩니다.
다음으로, mRNA는 RNA 결합 단백질과 결합하여 리보핵입자로 알려진 복합체를 형성해야 합니다. 이 과정은 고도로 조절되며, 리보핵입자에 존재하는 mRNA만이 핵에서 세포질로 운반되어 번역될 수 있습니다.
번역 제어는 유전자 발현 조절을 위한 또 다른 중요한 포인트입니다. 조절은 개별 또는 하위 집합 mRNA가 관여하는 경우 구체적일 수도 있고, 대부분의 mRNA 전사체가 영향을 받는 경우 일반적일 수도 있습니다. 
특정 조절에서 번역 억제는 단백질 및 microRNA 및 짧은 간섭 RNA를 포함한 특정 유형의 RNA와 같은 trans-acting elements와의 상호 작용을 통해 제어됩니다.
일반적으로 번역 기계에 관여하는 다양한 단백질이 활성화되거나 억제되어 모든 전사체에 영향을 미칩니다.
마지막으로, 인산화(phosphorylation)와 같은 번역 후 변형(post-translational modification)은 단백질을 활성화하거나 비활성화할 수 있는 반면, 유비퀴틴화(ubiquitination)와 같은 다른 변형은 단백질의 분해를 초래할 수 있습니다.

<ol>
	<li>Alberts et al., 6판; 372페이지</li>
	<li>Lodish H, Berk A, Zipursky SL, et al. 분자 세포 생물학.4판. 뉴욕: W. H. 프리먼; 2000. 섹션 11.3, mRNA 처리 규정.</li>
	<li>Valencia-Sanchez, M. A., Liu, J., Hannon, G. J., & Parker, R. (2006). miRNA 및 siRNA에 의한 번역 및 mRNA 분해 제어. 유전자 및 발달, 20(5), 515-524.</li>
	<li>Lei, E. P., & Silver, P. A. (2002). 단백질과 RNA는 핵에서 내보내집니다. 발달 세포, 2(3), 261-272.</li>
	<li>Hershey, John W B et al. "Principles of translational control: an overview." 생물학의 콜드 스프링 하버 관점 vol. 4,12 a011528. 2012년 12월 1일, doi:10.1101/cshperspect.a011528</li>
</ol>

발현 조절은 여러 단계에서 발생합니다

Regulation of Expression Occurs at Multiple Steps

유전자 발현은 유전자에서 단백질까지 거의 모든 단계에서 조절될 수 있습니다. 전사는 가장 일반적으로 규제되는 단계입니다. 이는 DNA의 짧은 조절 서열에 단백질이 결합하는 것을 포함합니다. 이러한 연관은 각각의 서열과 연관된 유전자의 전사를 촉진하거나 억제할 수 있습니다.

전사를 통해 엑손과 인트론으로 구성된 전구체(pre-mRNA)가 생성되며, 이는 단백질로 번역되기 전에 추가 처리가 필요합니다. 이는 비코딩 영역을 제거하고 코딩 영역을 병합하는 mRNA 접합을 통해 발생합니다. mRNA 처리는 특정 엑손 건너뛰기, 대체 접합 및 인트론 포함과 같은 접합 패턴의 변화를 통해 조절 메커니즘으로 사용될 수도 있습니다.

3' 말단에 폴리-A 꼬리를 추가하고 성숙한 mRNA를 생성하기 위한 5' 캡을 추가하는 것도 RNA 처리 중 조절 지점입니다. 조절은 폴리아데닐화 신호의 변화를 통해 발생하며, 이는 폴리-A 꼬리가 mRNA에 추가되는 위치를 결정합니다. 어떤 경우에는 3' 말단에 하나 이상의 폴리-A 신호가 존재하여 3' 번역되지 않은 영역의 길이가 변경되지만 최종 단백질 생성물은 동일합니다. 그러나 변이체 mRNA의 안정성과 번역 가능성이 다를 수 있으며, 이는 생산되는 단백질의 양을 변경할 수 있습니다. 다른 경우에는 추가적인 폴리-A 신호가 유전자 서열 내의 인트론이나 엑손에 존재하여 폴리아데닐화를 위한 스플라이싱 부위의 변화를 유도하고 동일한 pre-mRNA 가닥에서 다른 단백질을 생성할 수 있습니다. 메틸화된 구아노신으로 구성된 캡은 두 가지 메커니즘으로 조절됩니다. 하나는 구아노신에 메틸기를 추가하는 메틸트랜스퍼라제의 조절과 관련이 있고, 다른 하나는 메틸화를 유도하는 세포 신호 전달 경로의 조절을 통한 것입니다.

다음으로, 성숙한 mRNA는 번역되기 위해 핵 기공 복합체(NPC)를 통해 핵에서 세포질로 운반되어야 합니다. 이는 mRNA에 의해 조절되어 RNA 결합 단백질과 함께 리보핵입자로 알려진 복합체를 형성합니다. NPC는 복합체에 있는 mRNA가 세포질로 전달되는 것을 허용합니다. mRNA가 번역을 위해 세포질에 들어가면 특정 규정을 통해 개별적으로 또는 그룹의 일부로 표적화될 수 있거나 세포질의 다른 모든 mRNA와 공통 규정을 겪을 수 있습니다. 특정 조절에서는 단백질 및 다양한 유형의 RNA와 같은 특정 트랜스 작용 요소가 전사를 조절합니다. 일반적인 조절에서는 번역 기계에 관여하는 단백질이 활성화되거나 억제되며, 이는 결국 모든 전사체의 번역에 영향을 미칩니다. 가장 일반적인 번역 조절 메커니즘은 번역 개시 인자의 수정입니다.

유전자 발현은 또한 번역 후 변형을 통해 조절될 수 있으며, 여기서 효소 촉매에 의한 가역적 변형은 단백질의 기능을 변경할 수 있습니다. 일반적인 번역 후 변형은 인산화이며, 이는 키나제라고 알려진 효소에 의해 수행됩니다. 반면, 단백질의 탈인산화는 포스파타제라고 알려진 단백질에 의해 수행됩니다. 단백질의 인산화는 단백질의 활성화 또는 비활성화를 초래하고 기능을 변경할 수 있습니다.

유전자 발현은 유전자에서 단백질에 이르는 거의 모든 단계에서 조절될 수 있습니다. 전사는 가장 일반적으로 규제되는 단계입니다. 이것은 다음을 포함합니다 ...

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

Education

교육

JoVE Core

Molecular Biology

분자생물학

Unit 1

제1단원

Gene Expression

유전자 발현

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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 분자생물학은 명확하고 간결한 애니메이션을 통해 분자 단계에서 일어나는 세포 과정을 설명합니다.또한, 과학자가 직접 실험을 진행하는 실사 영상을 통해 분자생물학 개념의 응용 사례를 보여줍니다.

How Cells Control Gene Expression

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