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Updated: Jan 29, 2026

ALS - Motor Neuron Disease: Mechanism and Development of New Therapies
Published on: July 29, 2007
FIR/PUF60: Multifunctional Molecule Through RNA Splicing for Revealing the Novel Disease Mechanism and Effective
Kazuyuki Matsushita1, Kouichi Kitamura1, Nobuko Tanaka1
1Department of Laboratory Medicine, Chiba University Hospital, Chiba 260-8677, Japan.
Abstract:
Disease-specific diversity in RNA transcripts stems from RNA splicing, ribosomal abnormalities, and other factors. However, the mechanisms underlying the regulation of rRNA expression in the nucleolus and mRNA expression in the cytoplasm during cancer and neuronal differentiation remain largely unknown. In this article, we review current knowledge and discuss the regulatory mechanisms of rRNA and mRNA expression in human diseases using the splicing model of PUF60 (poly(U) binding splicing factor 60)-also known as FUSE-binding protein-interacting repressor (FIR) (FUBP1-interacting repressor), RoBPI, SIAHBP1, and VRJS (Gene ID: 22827). Noncoding RNAs, much like coding RNAs, have been found to be translated into proteins with significant physiological functions. Splicing is also involved in dominant ORF RNAs implicated in the expression of both noncoding and coding RNAs. Here, we analyze recent findings regarding gene splicing, ribosome formation, and the determination of selected ORFs (dominant ORFs) in a system modeled on FIR splicing in two databases (RefSeq and ENSEMBL). rRNA transcription affects ribosomes, whereas mRNA expression and splicing affect the intracellular proteome. Our objective is to develop efficient methods for identifying biomarkers for disease diagnosis and therapeutic targets. In the field of cancer treatment, therapeutic drugs targeting intracellular signaling have proven effective.
Insights
This review explores how RNA splicing, particularly involving PUF60 (poly(U) binding splicing factor 60), regulates rRNA and mRNA expression in diseases. Understanding these mechanisms aids in identifying biomarkers and therapeutic targets for cancer.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Disease-specific RNA transcript diversity arises from splicing and ribosomal regulation.
- Mechanisms governing rRNA and mRNA expression in cancer and neuronal differentiation are poorly understood.
- PUF60 (poly(U) binding splicing factor 60), also known as FIR, plays a role in RNA splicing.
Purpose of the Study:
- To review current knowledge on rRNA and mRNA expression regulation in human diseases.
- To discuss regulatory mechanisms using the PUF60/FIR splicing model.
- To explore the role of splicing in dominant ORF RNAs and ribosome formation.
Main Methods:
- Analysis of recent findings on gene splicing and ribosome formation.
- Utilizing a system modeled on FIR splicing.
- Examination of RefSeq and ENSEMBL databases.
Main Results:
- rRNA transcription impacts ribosome biogenesis.
- mRNA expression and splicing influence the intracellular proteome.
- Splicing is implicated in dominant ORF RNAs, affecting both coding and noncoding RNA expression.
Conclusions:
- Elucidating FIR splicing mechanisms can reveal insights into disease-related RNA regulation.
- Identifying biomarkers for disease diagnosis and therapeutic targets is a key objective.
- Targeting intracellular signaling pathways shows promise in cancer treatment.
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