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Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
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Splicing to keep splicing: A feedback system for cellular homeostasis and state transition
Zhonghao Guo1,2, Xurui Zhang2, Yachen Li2,3
1Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Clinical and Translational Medicine
|June 20, 2025
Summary
Alternative splicing (AS) regulates gene expression by controlling splicing factors (SFs). This review explores how AS creates feedback loops, impacting cellular homeostasis and state transitions, with implications for diseases like ALS and cancer.
Area of Science:
- Molecular Biology
- Genetics
- Gene Regulation
Background:
- Alternative splicing (AS) generates proteomic diversity from single genes.
- Splicing factors (SFs) are increasingly recognized as targets of AS regulation.
- Understanding SF regulation by AS is crucial for comprehending gene expression control.
Purpose of the Study:
- To review mechanisms of SF regulation by AS.
- To examine feedback loops (autoregulation and inter-regulation) involving SFs.
- To discuss the biological implications of these regulatory networks.
Main Methods:
- Literature review focusing on SF autoregulation and inter-regulation.
- Analysis of mechanisms like AS-coupled nonsense-mediated mRNA decay (AS-NMD), nuclear retention, and alternative 3'UTR regulation.
- Exploration of the role of non-coding RNAs (circRNAs, microRNAs) in splicing networks.
Main Results:
- Negative feedback loops maintain cellular homeostasis.
- Positive feedback loops drive cellular state transitions.
- AS feedback mechanisms are implicated in diseases such as ALS, FTD, and cancer.
- Master SFs orchestrate splicing cascades impacting cellular processes.
- Integrated feedback networks with non-coding RNAs regulate gene expression.
Conclusions:
- AS regulation of SFs creates intricate feedback networks.
- These networks are essential for precise cell fate decisions.
- Further research into splicing regulatory networks holds therapeutic potential.
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