# SRSF9-Mediated Exon Recognition Promotes Exon 2 Inclusion in Mecp2 Pre-mRNA Alternative Splicing

**Authors:** Saya Oshizuki, So Masaki, Satoshi Tanaka, Naoyuki Kataoka

PMC · DOI: 10.3390/ijms26073319 · 2025-04-02

## TL;DR

This study explores how a specific protein, SRSF9, helps include a key part of the Mecp2 gene during protein production, which is important for a neurological disorder called Rett syndrome.

## Contribution

The study identifies SRSF9 as a key factor in the inclusion of exon 2 during Mecp2 pre-mRNA splicing.

## Key findings

- Exon 2 in Mecp2 pre-mRNA is efficiently recognized through adjacent strong splice sites.
- An exonic splicing enhancer in exon 2 is crucial for its inclusion, likely mediated by SRSF9.

## Abstract

Alternative splicing is one of the processes that contributes to producing a vast protein diversity from the limited number of protein-coding genes in higher eukaryotes. The Methyl CpG Binding Protein 2 (Mecp2) gene, whose mutations cause Rett syndrome, generates two protein isoforms, MeCP2E1 and MeCP2E2, by alternative splicing. These isoforms likely possess non-redundant functions. However, the molecular mechanism for Mecp2 pre-mRNA alternative splicing remains to be understood. Here, we analyzed the alternative splicing mechanism of MeCP2 pre-mRNA and found that exon 2 is efficiently recognized through adjacent strong splice sites. In addition, exonic splicing enhancer (ESE) in exon 2 plays an important role in exon 2 inclusion, which is highly likely to be mediated by SRSF9.

## Linked entities

- **Genes:** MECP2 (methyl-CpG binding protein 2) [NCBI Gene 4204]
- **Proteins:** Mecp2 (methyl CpG binding protein 2), SRSF9 (serine and arginine rich splicing factor 9)
- **Diseases:** Rett syndrome (MONDO:0010726)

## Full-text entities

- **Genes:** SRSF9 (serine and arginine rich splicing factor 9) [NCBI Gene 8683] {aka SFRS9, SRp30c}, MECP2 (methyl-CpG binding protein 2) [NCBI Gene 4204] {aka AUTSX3, MRX16, MRX79, MRXS13, MRXSL, PPMX}
- **Diseases:** Rett syndrome (MESH:D015518)

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11989674/full.md

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Source: https://tomesphere.com/paper/PMC11989674