# FIR/PUF60: Multifunctional Molecule Through RNA Splicing for Revealing the Novel Disease Mechanism and Effective Individualized Therapies

**Authors:** Kazuyuki Matsushita, Kouichi Kitamura, Nobuko Tanaka, Sohei Kobayashi, Yusuke Suenaga, Tyuji Hoshino

PMC · DOI: 10.3390/ijms27020643 · 2026-01-08

## TL;DR

This paper explores how RNA splicing, particularly through the PUF60/FIR molecule, influences disease mechanisms and could lead to better individualized therapies.

## Contribution

The paper introduces a novel splicing model of PUF60/FIR to explore RNA regulation in diseases, focusing on biomarker identification and therapeutic targets.

## Key findings

- PUF60/FIR splicing model is linked to regulation of rRNA and mRNA in diseases.
- Noncoding RNAs can be translated into functional proteins, impacting disease mechanisms.
- Dominant ORFs in spliced RNA may serve as potential biomarkers for disease diagnosis.

## 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.

## Linked entities

- **Genes:** PUF60 (poly(U) binding splicing factor 60) [NCBI Gene 22827], FARP2 (FERM, ARH/RhoGEF and pleckstrin domain protein 2) [NCBI Gene 9855], FUBP1 (far upstream element binding protein 1) [NCBI Gene 8880], PUF60 (poly(U) binding splicing factor 60) [NCBI Gene 22827], PUF60 (poly(U) binding splicing factor 60) [NCBI Gene 22827]

## Full-text entities

- **Genes:** PUF60 (poly(U) binding splicing factor 60) [NCBI Gene 22827] {aka FIR, RoBPI, SIAHBP1, VRJS}
- **Diseases:** cancer (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12841381/full.md

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Source: https://tomesphere.com/paper/PMC12841381