Alternative splicing in the RBMXL1 5'-UTR induces uORF-mediated translation control in activated B lymphocytes

Area of Science:

• Molecular Biology
• Gene Regulation

Background:

• The RNA binding motif X-linked (RBMX) gene is crucial for gene transcription and alternative splicing, with altered expression linked to cancers.
• RBMX-like genes (RBMXLs), including RBMXL1, arose from RBMX retrotransposition and share high protein identity, suggesting similar functions.

Purpose of the Study:

• To investigate alternative splicing variations in the RBMXL1 gene.
• To determine the functional impact of a specific alternative splicing event in RBMXL1 mRNA.

Main Methods:

• Analysis of alternative splicing in human RBMXL1 mRNA.
• Investigation of RBMXL1 mRNA splicing following Epstein-Barr virus (EBV) infection or B lymphocyte activation.
• Functional assessment of the upstream open reading frame (uORF) generated by alternative splicing.

Main Results:

• A specific alternative splicing event was identified in the 5'-untranslated region of human RBMXL1 mRNA.
• This splicing variation, observed after EBV infection or B cell activation, introduces a small exon.
• The resulting RBMXL1 uORF was found to be functional, downregulating the translation of the primary downstream open reading frame.

Conclusions:

• The identified alternative splicing of RBMXL1 generates a functional uORF that represses downstream translation.
• This regulatory mechanism likely plays a role in fine-tuning the cellular levels of RBMX and RBMXL1 proteins.