Vascular smooth muscle cell RNA-binding protein U2AF2 induces copper death by regulating C1qbp expression, delaying

Yang Yang1, Hongxu Chen1, Qijun Yu1

  • 1Department of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23, Postal Street, Nangang District, Harbin, 150001, Heilongjiang, China.

Biological Research
|January 29, 2026
PubMed
Abstract

Insights

This study uncovers how U2AF2, C1qbp, and NEAT1 regulate copper death in atherosclerosis. Targeting U2AF2 shows promise for treating this cardiovascular disease.

Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • Cell Death Mechanisms

Background:

  • Atherosclerosis (AS) is a primary cause of cardiovascular and cerebrovascular diseases.
  • Vascular smooth muscle cell (VSMC) phenotypic changes and death are critical in AS development.
  • Understanding molecular regulators of cell death in AS is essential.

Purpose of the Study:

  • To elucidate the molecular mechanisms of the U2AF2-C1qbp-copper death axis in AS.
  • To investigate the role of the NEAT1 lncRNA in this regulatory network.
  • To evaluate U2AF2 as a therapeutic target for AS.

Main Methods:

  • Construction of an ApoE-/- mouse model induced by high-fat diet.
  • Application of cell culture, molecular biology, immunology, and histology techniques.
  • Utilized qRT-PCR, Western blot, immunoprecipitation, RNA pull-down, and RIP assays.

Main Results:

  • Elevated copper ion levels and altered cuproptosis gene expression observed in AS models.
  • U2AF2 enhances C1qbp expression, promoting DLAT oligomerization and cuproptosis.
  • NEAT1 scaffolds U2AF2-C1qbp mRNA interaction, facilitating the process.
  • Targeted U2AF2 inhibition improved AS pathology and lipid profiles.

Conclusions:

  • The U2AF2-C1qbp-copper death axis is implicated in AS development.
  • This axis offers novel therapeutic targets for AS.
  • Targeted inhibition of U2AF2 presents a potential strategy to mitigate AS progression.

Related Concept Videos

Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
26.4K
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
11.0K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
7.3K
Functions of Smooth Muscles01:23

Functions of Smooth Muscles

Smooth muscles are an important type of muscle tissue that plays a vital role in the involuntary movements of internal organs. For example, they help regulate the movement of food through the gut and the flow of blood through the circulatory system.
Function of visceral smooth muscles
Visceral smooth muscle is found in the walls of all hollow organs, except the heart, and is a key player in the involuntary movements that drive the functioning of these internal organs. This tissue is arranged in...
3.4K
Smooth Muscle Contraction01:25

Smooth Muscle Contraction

Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
7.7K
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.8K