Nonsense mediated decay
Encyclopedia
Nonsense-mediated decay is a cellular
mechanism of mRNA
surveillance that functions to detect nonsense mutations and prevent the expression of truncated or erroneous proteins. Following transcription
, precursor mRNA
undergoes an assemblage of ribonucleoprotein
(RNP) components followed by regulatory pre-mRNA processing. Large average intron
size in eukaryotic cells greatly increases the probability that aberrant mRNA splicing will result in the presence of a nonsense (stop) codon
(UAA, UAG, UGA) somewhere within the open reading frame
. NMD is triggered by exon junction complex
es (EJCs) (components of the assembled RNP) that are deposited during pre-mRNA processing. While EJCs located in an open reading frame upstream of exon-exon junctions may facilitate ribosomal
recruitment prior to displacement by a "pioneer" round of translation, EJCs located downstream of a nonsense codon are not displaced because the ribosome is released from the transcript before reaching it. These remaining EJCs function as tags for recruitment of UPF1
following the mRNA's transport out of the nucleus and into the cytosol where the RNA is degraded, for example by the exosome complex
. NMD is not only a mechanism for degrading aberrant mRNA, however, as there are numerous examples of normal transcripts whose expression is regulated by this process including the plasticity protein Arc/Arg3.1.
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
mechanism of mRNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
surveillance that functions to detect nonsense mutations and prevent the expression of truncated or erroneous proteins. Following transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
, precursor mRNA
Precursor mRNA
Precursor mRNA is an immature single strand of messenger ribonucleic acid . pre-mRNA is synthesized from a DNA template in the cell nucleus by transcription. Pre-mRNA comprises the bulk of heterogeneous nuclear RNA...
undergoes an assemblage of ribonucleoprotein
Ribonucleoprotein
Ribonucleoprotein is a nucleoprotein that contains RNA, i.e. it is an association that combines ribonucleic acid and protein together. A few known examples include the ribosome, the enzyme telomerase, vault ribonucleoproteins, and small nuclear RNPs , which are implicated in pre-mRNA splicing and...
(RNP) components followed by regulatory pre-mRNA processing. Large average intron
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
size in eukaryotic cells greatly increases the probability that aberrant mRNA splicing will result in the presence of a nonsense (stop) codon
Nonsense mutation
In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete, and usually nonfunctional protein product. It differs from a missense mutation, which is a point mutation...
(UAA, UAG, UGA) somewhere within the open reading frame
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...
. NMD is triggered by exon junction complex
Exon junction complex
The exon junction complex has major influences on translation, surveillance and localization of the spliced mRNA. It is first deposited onto mRNA during splicing and is then transported into the cytoplasm. There it plays a major role in post-transcriptional regulation of mRNA. It is believed that...
es (EJCs) (components of the assembled RNP) that are deposited during pre-mRNA processing. While EJCs located in an open reading frame upstream of exon-exon junctions may facilitate ribosomal
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
recruitment prior to displacement by a "pioneer" round of translation, EJCs located downstream of a nonsense codon are not displaced because the ribosome is released from the transcript before reaching it. These remaining EJCs function as tags for recruitment of UPF1
UPF1
Regulator of nonsense transcripts 1 is a protein that in humans is encoded by the UPF1 gene.-Interactions:UPF1 has been shown to interact with UPF2, SMG1, DCP2, DCP1A, UPF3A and UPF3B.-Further reading:...
following the mRNA's transport out of the nucleus and into the cytosol where the RNA is degraded, for example by the exosome complex
Exosome complex
The exosome complex is a multi-protein complex capable of degrading various types of RNA molecules...
. NMD is not only a mechanism for degrading aberrant mRNA, however, as there are numerous examples of normal transcripts whose expression is regulated by this process including the plasticity protein Arc/Arg3.1.