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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.
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Nonsense-mediated mRNA Decay

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Nuclear Export of mRNA

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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...

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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...

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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.
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Updated: Dec 5, 2025

Monitoring Protein-RNA Interaction Dynamics In Vivo at High Temporal Resolution Using χCRAC

Monitoring Protein-RNA Interaction Dynamics In Vivo at High Temporal Resolution Using χCRAC

Published on: May 9, 2020

The NBDY Microprotein Regulates Cellular RNA Decapping.

Zhenkun Na^1,2, Yang Luo^1,2, Jeremy A Schofield^2,3

¹Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States.

|October 16, 2020

Summary

This summary is machine-generated.

Newly discovered microproteins, like NBDY, regulate cellular processes. This study reveals NBDY

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Area of Science:

Molecular Biology
Genomics
Cell Biology

Background:

Microproteins, short polypeptides (<100 amino acids), are increasingly recognized for their regulatory roles.
NBDY is a microprotein component of the human cytoplasmic RNA decapping complex.
Previous studies showed NBDY regulates P-bodies and reporter gene stability, but its endogenous function was unclear.

Purpose of the Study:

To investigate the global effect of endogenous NBDY on the cellular transcriptome.
To elucidate the mechanism by which NBDY regulates RNA stability.

Main Methods:

Proteogenomic identification of microproteins.
Generation of NBDY knockout (KO) cell lines.
Global RNA stability profiling using RNA sequencing.
Analysis of transcript half-lives and correlation with 5' UTR length.
Investigation of nonsense-mediated decay pathway involvement.

Main Results:

Endogenous NBDY interacts with the RNA decapping complex (EDC4, DCP1A) and localizes to P-bodies.
NBDY knockout cells exhibit dysregulated stability of over 1400 transcripts.
DCP2 substrate transcript half-lives are altered in NBDY KO cells, correlating with 5' UTR length.
NBDY deletion affects non-DCP2 target transcript stability, potentially via nonsense-mediated decay factors.

Conclusions:

NBDY plays a significant endogenous role in regulating cellular RNA stability.
NBDY's interaction with the decapping complex is crucial for its function.
A comprehensive model for NBDY-mediated RNA stability regulation is proposed.