Name: boosting protein translation fidelity
Uploaded: 2023-04-30T18:28:45.000Z
Duration: 2 min 7 s
Channel: JoVE

K12 Standards

Virginia  Standards of Learning

HIgh School

Biology

BIO.2

BIO.2.d

Improving Translational Accuracy

A single eukaryotic mRNA is translated to yield a typical-sized protein in about 30&#8211;60 seconds.
During this process, translation accuracy is maintained by elongation factors, EF-Tu and EF-G in bacteria, and EF1 and EF2 in eukaryotes.
During translation, EF-Tu associates with GTP and aminoacyl-tRNA. Together, they bind the A site of the ribosome to form a codon-anticodon duplex.
Each codon&#8211;anticodon interaction is checked twice.
The first checkpoint is the complementary base pairing between the mRNA codon and the tRNA anticodon.
A correct codon&#8211;anticodon match binds more tightly than an incorrect tRNA, which will dissociate.
At the second checkpoint, part of the 16S rRNA in the small ribosomal subunit folds around the paired bases forming a network of ribosomal contacts that are specific for each position of the codon&#8211;anticodon.&#160;
A mismatched tRNA fails to make ribosomal contacts, and dissociates, while the correct tRNA changes the conformation of the catalytic center within the ribosome. This is called an induced fit.
This causes EF-Tu to hydrolyze GTP and dissociate from the ribosome. The released aminoacyl-tRNA can now participate in translation.
If an aminoacyl-tRNA escapes proo

improving translational accuracy

Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in organisms are significantly lower.
The high level of accuracy is guaranteed by two additional proofreading steps involving two principles from enzyme-substrate interactions.
Within the ribosome, the peptidyl transferase center (PTC) catalyzes the covalent bond formation between amino acids to form a polypeptide chain. Like any other enzyme, the PTC also has an active site that discriminates between substrates based on their molecular structure. Residues from the 16S rRNA of the small ribosomal subunit form hydrogen bonds with the base and backbone atoms of the codon-anticodon duplex. Only the correct tRNA can induce conformational changes in the PTC, which carries out the catalysis.
The second step, called kinetic proofreading, occurs after the irreversible dissociation of EF-Tu&#183;GDP from the ribosome. GTP hydrolysis marks the start of a short time delay during which the aminoacyl-tRNA moves into the active site of PTC for catalysis. During this delay, any incorrect codon-anticodon pairs that slipped through the induced-fit step are more likely to dissociate than correct pairs. The reason for this is that the wrong tRNA makes weaker base pairs with the codon, and the time delay is longer for incorrect than correct matches.

Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single ...

Education

JoVE Core

Cell Biology

Unit 1

Translation: RNA to Protein

KEY TERMS AND CONCEPTS

boosting protein translation fidelity

Protein translation fidelity helps cells build the right protein from an mRNA message. The ribosome must read each codon correctly and add the matching amino acid in order. Even small errors can change the final protein.

The transcript explains how accuracy can be improved during translation. It focuses on the steps that help the ribosome choose the correct tRNA and keep the growing peptide chain on track. These controls reduce mistakes while the protein is being made.

This topic is important for understanding how cells make proteins with precision. It also shows how the translation process depends on careful matching at each step. When this matching is improved, the protein product is more likely to be correct.

Boosting Protein Translation Fidelity

translation

How Cells Build Proteins from mRNA

Translation is the cell process that builds proteins from messenger RNA, or mRNA. It comes after transcription and is the final step in gene expression. Ribosomes, which are made of protein and specialized RNA, carry out this process with help from transfer RNA, or tRNA, and other proteins. The result is a chain of amino acids called a polypeptide. Proteins are called the building blocks of life because they make up much of an organism, from muscle fibers and hair to parts of the immune system.

ribosomes

Ribosomes in Protein Synthesis

Ribosomes build proteins by reading messenger RNA, or mRNA, and turning that genetic code into an amino acid chain. Both prokaryotic and eukaryotic cells have ribosomes. Cells that make large amounts of protein, such as secretory cells in the human pancreas, can contain millions of them. Ribosomes are made of ribosomal RNA, or rRNA, and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus, a region of the nucleus that specializes in making ribosomes. There, rRNA joins with...

trna activation

Charging tRNA for Protein Synthesis

tRNA charging is the step that prepares transfer RNA for protein synthesis. In this process, an amino acid is attached to its matching tRNA by an enzyme called aminoacyl-tRNA synthetase. The charged tRNA can then deliver that amino acid during translation. tRNA charging is a key part of how cells build proteins from genetic information. The transcript focuses on the activation of tRNA and the role of aminoacyl-tRNA synthetases in this process. These enzymes help ensure that the correct amino...

initiation of translation

Translation Begins with Ribosome Assembly

Translation begins when a ribosome assembles on an mRNA molecule and starts reading its code. During this first stage of protein synthesis, the cell prepares the machinery needed to build a protein from amino acids. The small ribosomal subunit binds to the mRNA first. It helps position the message so the ribosome can find the correct start site. Then the initiator tRNA, which carries the first amino acid, pairs with the start codon on the mRNA. After the start codon is matched, the large...

termination of translation

How Protein Synthesis Ends

Protein synthesis ends when translation reaches a stop signal on the mRNA. At this stage, the ribosome no longer adds amino acids to the growing polypeptide chain. Instead, the process shifts to releasing the completed protein.

Protein translation fidelity helps cells build the right protein from an mRNA message. The ribosome must read each codon correctly and add the matching amino acid in order. Even small errors can change the final protein. The transcript explains how accuracy can be improved during translation. It focuses on the steps that help the ribosome choose the correct tRNA and keep the growing peptide chain on track. These controls reduce mistakes while the protein is being made. This topic is important...

nonsense-mediated mrna decay

Nonsense-Mediated mRNA Decay and UPF Proteins

Nonsense-mediated mRNA decay is a cell quality-control process that removes faulty mRNA before it can make a shortened protein. It helps protect cells from errors during gene expression. The pathway depends on UPF proteins, which help identify and trigger the breakdown of the problem message. This process matters when an mRNA contains a premature stop signal, also called a nonsense codon. Instead of allowing translation to continue, the cell recognizes the defective message and targets it for...

molecular chaperones and protein folding

Chaperones Guide Protein Folding

Molecular chaperones help proteins fold into the correct shape. Protein folding is a key step after a protein is made, because shape affects function. If a protein does not fold properly, it may not work as it should. Chaperones do not become part of the final protein. Instead, they assist the folding process and help proteins avoid harmful misfolding. They are especially important when newly made proteins are still fragile and need support as they take on their proper structure. This topic...

the proteasome

Protein Recycling by the Proteasome

The proteasome breaks down proteins inside cells. It helps control which proteins stay active and which are removed. This process is an important part of protein recycling. Proteins can be tagged for destruction before they enter the proteasome. The cell uses this system to remove proteins that are no longer needed or that must be cleared away. The proteasome then cuts them into smaller pieces. This protein breakdown helps the cell stay organized and function properly. By clearing selected...

regulated protein degradation

How Cells Remove Unneeded Proteins

Cells remove unneeded proteins through regulated protein degradation. This process helps control which proteins stay active and which proteins are broken down. Protein degradation is not random. The cell uses signals to mark proteins for removal at the right time. This regulation lets the cell respond to changing needs and keep protein levels balanced. Regulated protein degradation is an important part of molecular biology. It shows how cells maintain control over their internal processes by...

proteins: from genes to degradation

Protein Synthesis and Breakdown

Proteins are made from genes and later broken down when they are no longer needed. This page follows that path from gene information to protein degradation, or protein breakdown. It shows how cells build proteins and how they remove them at the right time. The process begins with genes, which carry the instructions for making proteins. Those instructions are used to produce proteins with specific jobs in the cell. After a protein has done its work, the cell can degrade it instead of keeping it...

key terms and concepts

Learn how translation fidelity is improved as ribosomes match codons with tRNAs and build proteins with fewer errors in cells.

Boosting Protein Translation Fidelity | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

Alabama Course of Study Science

9-12

from-molecules-to-organisms-structures-and-processes

From Molecules to Organisms: Structures and Processes

9-12.B.1.2

Florida Department of Education

High School

Life Science

SC.912.L.16

SC.912.L.16.5

Functions of Life

Human life is characterized by a variety of functions that are essential for survival and well-being. These functions include metabolism, movement, ...

Requirements for Human Life

The Earth and its atmosphere have provided humans with air, water, and food, but these are not the only requirements for survival. Humans also require a ...

What is Homeostasis?

Maintaining homeostasis requires that the body continuously maintain its internal conditions. Each physiological condition has a particular set point, ...

Negative and Positive Feedback

Homeostatic Imbalance

Homeostasis is the maintenance of a stable internal environment within the body, which is crucial for the proper functioning of cells, tissues, organs, ...

Role of Water in Human Biology

Water is the one of the most significant components of the human body; it plays a crucial role in several physiological activities because of its unique ...

Introduction to Electrolytes

In humans, electrolytes play a vital role in various physiological processes. Balancing electrolyte levels is essential for normal body functions; their ...

pH Homeostasis

Acid-base homeostasis is essential for maintaining normal physiological activities in humans. The pH of various body fluids is strictly regulated because ...

The student will investigate and understand that chemical and biochemical processes are essential for life. Key ideas include water chemistry has an influence on life processes;

BIO.2.a

Compounds Essential to Human Function

The human body is composed of cells that are fundamentally made up of several different molecules. These molecules are essential to carry out all ...

Macromolecules

Biomolecules
Organisms contain a wide variety of organic molecules with numerous functions which depend on the chemical structures and properties of these ...

Solution Preparation
ExpandCAUTION: It is important to always use care when handling reagents. For example, iodine will stain clothes and skin so wear ...

Identifying Macromolecules with Indicator Solutions
ExpandHYPOTHESES: In this activity, the experimental hypothesis might be that the addition of an ...

pH Regulation in Cells

pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge ...

Chemistry of the Cell

Overview of Functional Groups

Functional groups are a group of atoms with characteristic properties, which when linked to the carbon skeleton of a molecule, alter the properties of ...

Introduction to Carbohydrates

Carbohydrates, proteins, and fats are the primary macronutrients in the human diet. However, carbohydrates are the most favored source of energy in the ...

Carbohydrate Metabolism

Sugars as Energy Storage Molecules

What are Lipids?

lipid-derived-compounds-in-the-human-body

Lipid-derived Compounds in the Human Body

Fats and lipids are crucial components in the human body. Some lipid-derived compounds, such as fat-soluble vitamins, eicosanoids, lipoproteins, and ...

Fats as Energy Storage Molecules

What are Proteins?

Protein Organization

Globular Proteins

In organisms, proteins are the most abundant macromolecules. They act as the building blocks of life and play various crucial roles in the body. Proteins ...

Fibrous Proteins

Fibrous proteins are either long and narrow proteins or assemble to form long and thin structures. They contain repetitive units and usually consist of ...

Protein Denaturation

The function of proteins depends on their native three-dimensional structure, which is dictated by the amino acid sequence of the specific protein. ...

Role of Proteins in the Human Body

Proteins are the building block of life. They are also&#160; the most abundant macromolecules with as many diverse roles in the body. They are part of ...

Nucleic Acids and Nucleotides

Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell&#39;s genetic blueprint and have instructions for its ...

Nucleic Acid Structure

The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group ...

ATP Energy Storage and Release

ATP and Macromolecule Synthesis

Biological macromolecules are organic compounds, predominantly composed of carbon atoms. The carbon atoms are covalently bonded with hydrogen, oxygen, ...

The student will investigate and understand that chemical and biochemical processes are essential for life.Key ideas include  macromolecules have roles in maintaining life processes;

BIO.2.b

structural-organization-of-the-human-body-an-overview

Structural Organization of the Human Body: An Overview

It is convenient to consider the body&#39;s structures in terms of fundamental levels of organization that increase in complexity: subatomic particles, ...

Introduction to Enzymes

The use of enzymes by humans dates to 7000 BCE. Humans first used enzymes to ferment sugars and produce alcohol without knowing that this was an ...

Enzymes and Activation Energy

The activation energy (or free energy of activation), abbreviated as Ea, is the small amount of energy input necessary for all chemical reactions to ...

Introduction to Enzyme Kinetics

Enzyme kinetics studies the rates of biochemical reactions. Scientists monitor the reaction rates for a particular enzymatic reaction at various substrate ...

Turnover Number and Catalytic Efficiency

The turnover number of an enzyme is the maximum number of substrate molecules it can transform per unit time. Turnover numbers for most enzymes range from ...

Catalytically Perfect Enzymes

The theory of catalytically perfect enzymes was first proposed by W.J. Albery and J. R. Knowles in 1976. These enzymes catalyze biochemical reactions at ...

introduction-to-mechanisms-of-enzyme-catalysis

Introduction to Mechanisms of Enzyme Catalysis

For many years, scientists thought that enzyme-substrate binding took place in a simple &#34;lock-and-key&#34; fashion. This model stated that the enzyme ...

Ligand Binding and Linkage

Cooperative Allosteric Transitions

Ribozymes

The student will investigate and understand that chemical and biochemical processes are essential for life. Key ideas include  enzymes have a role in biochemical processes;

BIO.2.c

What are Cells?

Cells are the smallest and basic units of life, whether it is a single cell that forms the entire organism, e.g., in a bacterium, or trillions of them, ...

The Nucleus

The nucleus is a membrane-bound organelle that acts as a control center in a eukaryotic cell. It contains chromosomal DNA, which controls gene expression ...

The DNA Helix

Deoxyribonucleic acid, or DNA, is the genetic material responsible for passing traits from generation to generation in all organisms and most viruses. DNA ...

The Central Dogma

The central dogma explains the flow of genetic information from DNA nucleotides to the amino acid sequence of proteins.
RNA is the Missing Link Between ...

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations ...

DNA as a Genetic Template

Structure of a Gene

A gene is the fundamental unit of heredity. Every individual has two copies of each gene, one inherited from each parent. Although most people contain the ...

Chromosome Structure

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised&#160; of nucleotides and proteins are ...

RNA Structure

The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form ...

Types of RNA

Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse ...

Transcription

Transcription is the synthesis of RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. ...

Bacterial RNA Polymerase

Eukaryotic RNA Polymerases

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of ...

RNA Polymerase II Accessory Proteins

Transcription Elongation Factors

pre-mrna-processing-modification-of-pre-mrna-ends

Pre-mRNA Processing: Modification of pre-mRNA Ends

In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or ...

Pre-mRNA Processing: RNA Splicing

Chromatin Structure and RNA Splicing

Alternative RNA Splicing

Nuclear Export of mRNA

Transfer RNA Synthesis

Ribosomal RNA Synthesis

The Nucleolus

Additional Subnuclear Structures

Translation

Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes ...

Ribosomes

Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that ...

tRNA Activation

Initiation of Translation

Termination of Translation

Nonsense-mediated mRNA Decay

Molecular Chaperones and Protein Folding

The Proteasome

Regulated Protein Degradation

Proteins: From Genes to Degradation

The student will investigate and understand that chemical and biochemical processes are essential for life. Key ideas include protein synthesis is the process of forming proteins which influences inheritance and evolution; and

Light as Energy

The energy required to carry out photosynthesis is light&#x2014; typically electromagnetic radiation from the sun. The range of all possible wavelengths ...

What is Photosynthesis?

All living organisms on Earth are directly or indirectly dependent on photosynthesis. It is the only biological process that can capture energy from ...

The Anatomy of Chloroplasts

Green algae and plants, including green stems and unripe fruit, harbor specialized organelles called chloroplasts to carry out photosynthesis. They ...

The student will investigate and understand that chemical and biochemical processes are essential for life. Key ideas include  the processes of photosynthesis and respiration include the capture, storage, transformation, and flow of energy.

BIO.2.e

Boosting Protein Translation Fidelity

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