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Nonsense-mediated mRNA Decay

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,...

Nonsense-mediated mRNA Decay

Nonsense-mediated mRNA Decay

Mutations

Mutations

Mutations

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 can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...

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RNA Splicing

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...

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Related Experiment Video

Updated: Apr 11, 2026

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

The BRCA2 polymorphic stop codon: stuff or nonsense?

J E Higgs¹, E F Harkness², N L Bowers¹

¹Manchester Centre for Genomic Medicine, Manchester Academic Health Sciences Centre, Institute of Human Development, University of Manchester and Central Manchester Foundation Trust, Manchester, UK.

Journal of Medical Genetics

|June 5, 2015

Summary

This summary is machine-generated.

The BRCA2 c.9976A>T variant, previously linked to cancers, is likely not pathogenic on its own. Its association with increased tumor risk is probably due to linkage disequilibrium with the pathogenic BRCA2 c.6275_6276delTT mutation.

Keywords:

BRCA2 polymorphic stop codon Cancer: breast Cancer: lung Cancer: oesophageal Cancer: pancreatic

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gDNA Enrichment by a Transposase-based Technology for NGS Analysis of the Whole Sequence of BRCA1, BRCA2, and 9 Genes Involved in DNA Damage Repair

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Published on: October 6, 2014

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Last Updated: Apr 11, 2026

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Published on: February 28, 2021

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gDNA Enrichment by a Transposase-based Technology for NGS Analysis of the Whole Sequence of BRCA1, BRCA2, and 9 Genes Involved in DNA Damage Repair

gDNA Enrichment by a Transposase-based Technology for NGS Analysis of the Whole Sequence of BRCA1, BRCA2, and 9 Genes Involved in DNA Damage Repair

Published on: October 6, 2014

Area of Science:

Genetics
Oncology
Molecular Biology

Background:

The BRCA2 c.9976A>T variant is classified as a polymorphism.
This variant has been anecdotally associated with increased risks for pancreatic, lung, esophageal, and breast cancers.

Purpose of the Study:

To investigate the potential association between the BRCA2 c.9976A>T variant and increased cancer risks.
To determine if co-occurrence with the BRCA2 c.6275_6276delTT mutation explains these observed cancer associations.

Main Methods:

A cohort study design was employed.
Co-occurrences of BRCA2 c.9976A>T and BRCA2 c.6275_6276delTT were analyzed.
Co-segregation analysis was performed in families.
Cancer frequencies in individuals with BRCA2 c.9976A>T alone were assessed using person-years at risk analysis.

Main Results:

Fifty-two families with the BRCA2 c.6275_6276delTT mutation were identified, all carrying BRCA2 c.9976A>T in cis.
Only 1.3% of 3245 sequenced breast/ovarian cancer samples carried BRCA2 c.9976A>T alone, after excluding individuals with BRCA2 c.6275_6276delTT or other pathogenic mutations.
No increased frequencies of esophageal, pancreatic, or lung cancer were found in families with only the BRCA2 c.9976A>T variant.

Conclusions:

The previously reported associations of increased cancer risks with BRCA2 c.9976A>T are likely due to reporting bias.
These associations are likely contributed to by the linkage disequilibrium (LD) between BRCA2 c.9976A>T and the pathogenic BRCA2 c.6275_6276delTT mutation.