Related Experiment Video

Updated: Sep 12, 2025

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
05:51

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

Published on: June 15, 2011

26.0K

Genetic disruption of nonsense-mediated mRNA decay in neurodevelopmental disorders

Saba Montazaribarforoushi1, Lachlan A Jolly2

  • 1Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia; Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.

Current Opinion in Genetics & Development
|August 7, 2025
PubMed

Insights

Nonsense-mediated mRNA decay (NMD) controls gene expression and quality. Gene variants impacting NMD are increasingly linked to neurodevelopmental disorders, suggesting NMD

Area of Science:

  • Molecular Biology
  • Genetics
  • Neuroscience

Background:

  • Nonsense-mediated mRNA decay (NMD) is a crucial cellular process for mRNA quality control and gene expression regulation.
  • NMD prevents the accumulation of aberrant transcripts with premature termination codons, safeguarding cellular function.
  • Disruptions in NMD pathways can have significant physiological consequences, as evidenced by embryonic lethality in NMD gene knockout models.

Purpose of the Study:

  • To review and synthesize current knowledge on NMD genes and their variants implicated in neurodevelopmental disorders (NDDs).
  • To highlight recent discoveries linking NMD dysfunction to the genetic basis of NDDs.
  • To assess the prevalence and significance of NMD gene involvement in NDDs.

Main Methods:

  • Literature review and data synthesis focusing on NMD genes and neurodevelopmental disorders.
  • Analysis of genetic databases and scientific literature for reported NMD gene variants associated with NDDs.
  • Comparative analysis of NMD gene involvement across different genetic causes of NDDs.

Main Results:

  • A significant proportion of NMD and NMD-related genes have been identified as contributors to human Mendelian diseases, particularly NDDs.
  • Over half of all NMD and NMD-related genes are implicated in NDDs, indicating a substantial enrichment.
  • Recent discoveries underscore the expanding role of NMD gene variants in the etiology of neurodevelopmental conditions.

Conclusions:

  • Compromised NMD function represents a convergent pathogenic mechanism in multiple genetic causes of NDDs.
  • The link between NMD and brain development warrants further investigation.
  • Understanding NMD's role is critical for diagnosing and potentially treating a spectrum of neurodevelopmental disorders.

More Related Videos

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae07:14

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae

Published on: February 25, 2022

6.1K
Generation of Topically Transgenic Rats by In utero Electroporation and In vivo Bioluminescence Screening08:44

Generation of Topically Transgenic Rats by In utero Electroporation and In vivo Bioluminescence Screening

Published on: September 24, 2013

14.0K

Related Concept Videos

Nonsense-mediated mRNA Decay02:27

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,...
10.8K
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.9K
mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
5.7K
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.7K
Translation01:31

Translation

Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
15.6K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.1K