Multi-step splicing of sphingomyelin synthase linear and circular RNAs

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• The SGMS1 gene encodes sphingomyelin synthase 1 (SMS1), crucial for lipid metabolism, apoptosis, and vesicular transport.
• Previous studies indicated numerous alternative SGMS1 transcripts across human tissues.
• SGMS1 is known to generate both protein-coding mRNAs and non-coding RNAs, including brain-enriched circular RNAs (circRNAs).

Purpose of the Study:

• To comprehensively identify novel transcripts of the SGMS1 gene using advanced sequencing technology.
• To investigate the role of recursive exons (RS-exons) in SGMS1 alternative splicing and circRNA formation.
• To elucidate the mechanisms generating diverse linear and circular RNAs from the SGMS1 gene.

Main Methods:

• High-throughput RNA-CaptureSeq technology was employed for comprehensive transcript identification.
• Bioinformatic analysis was used to characterize novel SGMS1 transcripts, including premature RNAs and alternatively spliced variants.
• Identification and analysis of recursive exons involved in SGMS1 splicing.

Main Results:

• Numerous new SGMS1 transcripts were discovered, encompassing intronic unspliced RNAs and products of alternative splicing.
• Recursive exons (RS-exons) participating in multi-step splicing of SGMS1 introns were identified.
• These RS-exons were found to contribute to the formation of SGMS1-derived circRNAs.

Conclusions:

• The SGMS1 gene generates a wide array of linear and circular RNA isoforms through complex and potentially multi-step splicing processes.
• The identification of RS-exons provides a mechanism for the generation of diverse RNA structures from a single gene.
• This complexity in RNA production highlights novel regulatory pathways in eukaryotic gene expression.