Name: nonsense-mediated mrna decay and upf proteins
Uploaded: 2023-04-30T18:28:45.000Z
Duration: 2 min 27 s
Channel: JoVE

K12 Standards

Virginia  Standards of Learning

HIgh School

Biology

BIO.2

BIO.2.d

Nonsense-mediated mRNA Decay

When an mRNA molecule is transported from the nucleus to the cytosol, as its 5&#697; end emerges from a nuclear pore, a ribosome begins to translate it.&#160;
This test translation checks the mRNA for errors and flags irregularly processed mRNAs for degradation.
In this mRNA surveillance mechanism, called the nonsense-mediated mRNA decay pathway, or NMD, the ribosome can detect if an mRNA molecule has a nonsense or stop codon in the wrong place.
Generally, a pre-mRNA can contain stop codons within introns, in addition to the intended stop codon. When this pre-mRNA is spliced and processed in the nucleus, exon junction complexes, or EJCs, bind the mRNA at each splice site.
In the test round of translation, the EJCs are displaced by the moving ribosome.&#160;
In a normally spliced mRNA, the stop codon, marked by the sequence UAA, UAG or UGA, lies within the last exon. So, when the ribosome reaches it and the translation is terminated, there are no bound EJCs.&#160;&#160;
Such an mRNA passes the quality check and is now available for further rounds of translation.
Incompletely spliced mRNAs still have nonsense codons present in the reading frame of the mRNA. This phenomenon is observed more frequently in orga

nonsense-mediated mrna decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA, Upf3 and EJC are displaced during translation. However, if there is a premature stop codon, Upf3 remains bound to EJC and marks the mutant mRNA for degradation.
Nonsense codon sequences may naturally occur in the intronic regions of an mRNA. However, a mutation can also produce a nonsense codon within a gene sequence. Such mutations are called nonsense mutations. As in the NMD pathway, these mutations also lead to premature termination of translation. The incomplete polypeptide synthesized is usually inactive. Normal function can be restored to the gene if a second mutation corrects the termination codon to an amino acid coding sequence, or suppresses the effects of the termination codon. These rectifying mutations are called nonsense suppressors. The most common nonsense suppressors are mutations in tRNA genes that produce specialized tRNAs called suppressor tRNAs. These can bind to the premature termination codon and insert an amino acid at that position.

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual ...

Education

JoVE Core

Cell Biology

Unit 1

Translation: RNA to Protein

KEY TERMS AND CONCEPTS

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 decay. In this way, nonsense-mediated mRNA decay limits the production of incomplete proteins that could interfere with normal cell function.

Nonsense-Mediated mRNA Decay and UPF Proteins

nonsense-mediated-mrna-decay-and-upf-proteins

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.

improving translational accuracy

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...

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 nonsense-mediated mRNA decay uses UPF proteins to detect faulty mRNA with premature stop signals and prevent shortened protein production.

Nonsense-Mediated mRNA Decay and UPF Proteins | 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

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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
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Identifying Macromolecules with Indicator Solutions
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pH Regulation in Cells

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Chemistry of the Cell

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Carbohydrate Metabolism

Sugars as Energy Storage Molecules

What are Lipids?

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Lipid-derived Compounds in the Human Body

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Fats as Energy Storage Molecules

What are Proteins?

Protein Organization

Globular Proteins

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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

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Role of Proteins in the Human Body

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Nucleic Acids and Nucleotides

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Nucleic Acid Structure

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ATP Energy Storage and Release

ATP and Macromolecule Synthesis

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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

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Structural Organization of the Human Body: An Overview

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Introduction to Enzymes

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Turnover Number and Catalytic Efficiency

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Catalytically Perfect Enzymes

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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

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DNA as a Genetic Template

Structure of a Gene

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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

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tRNA Activation

Initiation of Translation

Termination of Translation

Improving Translational Accuracy

Molecular Chaperones and Protein Folding

The Proteasome

Regulated Protein Degradation

Proteins: From Genes to Degradation

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Light as Energy

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BIO.2.e

Nonsense-Mediated mRNA Decay and UPF Proteins

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