Related Experiment Video

Updated: Jul 11, 2025

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications
10:12

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications

Published on: April 21, 2023

2.8K

K6-linked ubiquitylation marks formaldehyde-induced RNA-protein crosslinks for resolution

Aldwin Suryo Rahmanto1, Christian J Blum2, Claudia Scalera2

  • 1Institute of Molecular Biology (IMB), 55128 Mainz, Germany; Institute of Developmental Biology and Neurobiology (IDN), Johannes Gutenberg-Universität, 55128 Mainz, Germany.

Molecular Cell
|November 11, 2023
PubMed

Insights

Formaldehyde causes RNA-protein crosslinks (RPCs) that halt protein synthesis by stalling ribosomes. A cellular pathway involving RNF14 and VCP resolves these RPCs, mitigating aldehyde toxicity.

Area of Science:

  • Molecular Biology
  • Cellular Stress Response
  • Toxicology

Background:

  • Reactive aldehydes, byproducts of metabolism and alcohol consumption, can accumulate in tissues.
  • Aldehyde toxicity is primarily linked to DNA damage, inhibiting transcription and replication.
  • The role of aldehydes in interfering with other cellular processes remains largely unexplored.

Purpose of the Study:

  • To investigate whether reactive aldehydes interfere with cellular processes beyond DNA damage.
  • To elucidate the mechanism by which formaldehyde impacts protein synthesis.
  • To identify the cellular machinery involved in responding to formaldehyde-induced cellular damage.

Main Methods:

  • Utilized human cell models to study the effects of formaldehyde exposure.
  • Investigated formaldehyde-induced RNA-protein crosslinks (RPCs) and their impact on translation.
  • Characterized the ubiquitylation and resolution pathways involving RNF14 and VCP.

Main Results:

  • Demonstrated that formaldehyde induces RNA-protein crosslinks (RPCs) in human cells.
  • Showed that RPCs stall ribosomes, leading to the inhibition of translation.
  • Identified a pathway where RNF14 ubiquitinates RPCs, and VCP resolves them.

Conclusions:

  • Formaldehyde-induced RPCs contribute to cellular toxicity by inhibiting translation.
  • An evolutionarily conserved stress response pathway involving RNF14 and VCP protects cells from RPC accumulation.
  • These findings suggest a broader role for RPCs in the toxicity of reactive aldehydes.
Keywords:
K6-linked ubiquitylationRNA-protein crosslinksRNF14VCPquantitative proteomicsreactive aldehydesribosometranslation

More Related Videos

In Vitro Analysis of E3 Ubiquitin Ligase Function06:06

In Vitro Analysis of E3 Ubiquitin Ligase Function

Published on: May 14, 2021

5.3K
Detection of Protein Ubiquitination Sites by Peptide Enrichment and Mass Spectrometry11:54

Detection of Protein Ubiquitination Sites by Peptide Enrichment and Mass Spectrometry

Published on: March 23, 2020

9.6K

Related Concept Videos

Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
6.8K
Protein Modifications in the RER01:26

Protein Modifications in the RER

Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.2K
RNA Stability01:53

RNA Stability

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...
33.6K
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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...
920
Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.7K
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
7.0K