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Related Concept Videos

Nuclear Export of mRNA02:31

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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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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mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

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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.
Cis-acting Elements involved in mRNA stability
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RNA Stability01:53

RNA Stability

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Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
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Riboswitches01:56

Riboswitches

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Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
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Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Related Experiment Video

Updated: May 16, 2025

Monitoring Protein-RNA Interaction Dynamics In Vivo at High Temporal Resolution Using χCRAC
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A nuclear RNA degradation code is recognized by PAXT for eukaryotic transcriptome surveillance.

Lindsey V Soles1, Liang Liu1, Xudong Zou2

  • 1Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine, CA 92617, USA.

Molecular Cell
|April 5, 2025
PubMed
Summary
This summary is machine-generated.

Scientists discovered a nuclear RNA degradation code (NRDC) that targets specific RNA molecules for destruction. This mechanism, involving splice sites and poly(A) junctions, helps regulate RNA levels and is implicated in human diseases.

Keywords:
RNA degradationRNA exosomeRNA surveillancecleavage and polyadenylationgene expressionintronic polyadenylationpre-mRNA 3′ processingpre-mRNA splicingquality control

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Area of Science:

  • Molecular Biology
  • RNA Biology
  • Gene Regulation

Background:

  • The RNA exosome is crucial for eukaryotic RNA degradation, but its target recognition mechanisms are not fully understood.
  • The poly(A) tail exosome targeting (PAXT) pathway links the exosome to polyadenylated RNAs, particularly those with intronic poly(A) sites.

Purpose of the Study:

  • To elucidate the specific sequence requirements for PAXT-mediated RNA degradation.
  • To identify the molecular players involved in recognizing these sequences and recruiting the exosome.
  • To define a novel RNA degradation code and investigate its role in human diseases.

Main Methods:

  • Investigated RNA degradation triggered by combinations of 5' splice sites (ss) and poly(A) junctions (PAJ).
  • Assessed the binding of U1 small nuclear ribonucleoprotein particle (snRNP) and cleavage/polyadenylation factors to these sequences.
  • Examined the cooperative recruitment of PAXT by these factors.
  • Analyzed the impact of disease-associated single nucleotide polymorphisms creating novel 5' ss in 3' untranslated regions.

Main Results:

  • PAXT-mediated RNA degradation requires the combined presence of a 5' splice site and a poly(A) junction, not either sequence alone.
  • U1 snRNP and cleavage/polyadenylation factors bind to these sites and cooperatively recruit PAXT.
  • This 5' ss-PAJ combination, termed the nuclear RNA degradation code (NRDC), is absent in correctly processed RNAs.
  • Disease-associated SNPs creating new 5' ss in 3' UTRs can aberrantly trigger mRNA degradation via the NRDC mechanism.

Conclusions:

  • Identified the first nuclear RNA degradation code (NRDC) based on the 5' splice site-poly(A) junction combination.
  • Elucidated the recognition mechanism involving U1 snRNP, cleavage/polyadenylation factors, and PAXT recruitment.
  • Demonstrated the role of the NRDC in disease, particularly in aberrant mRNA degradation caused by genetic variations.