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

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.

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.

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