Complex tissue-specific patterns and distribution of multiple RAGE splice variants in different mammals

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• The receptor for advanced glycosylation end products (RAGE) is a key signaling molecule implicated in various biological processes and diseases.
• Alternative splicing (AS) significantly contributes to transcriptomic diversity and has evolutionary importance, yet RAGE AS in mammals remains understudied.
• Understanding RAGE AS is crucial for deciphering its functional roles and evolutionary trajectory.

Purpose of the Study:

• To comprehensively investigate the alternative splicing landscape of RAGE across six mammalian species.
• To identify and characterize novel RAGE splice variants, including noncoding transcripts.
• To analyze the tissue-specific expression patterns and evolutionary conservation of RAGE mRNA variants.

Main Methods:

• Nested reverse transcription-polymerase chain reaction (RT-PCR) was employed to detect RAGE splice variants in diverse tissues from six mammalian species.
• RNA-sequencing data analysis was used to identify abundant splice variants.
• Comparative analysis of identified variants across species and tissue types (fetal, adult, tumor) was performed.

Main Results:

• A large number of RAGE splice variants, including novel noncoding and predicted coding transcripts, were identified across six mammalian species.
• Over 80% of detected RT-PCR variants were novel, with 20-60% being noncoding and exhibiting tissue specificity.
• RNA-seq data primarily detected the most abundant splice variants, highlighting the sensitivity of RT-PCR for comprehensive variant discovery.
• Most identified RAGE splice variants were species-specific, with only two canonical variants conserved across all studied species.

Conclusions:

• RAGE undergoes extensive alternative splicing in mammals, generating significant transcriptomic diversity.
• The majority of RAGE splice variants are novel and species-specific, particularly noncoding variants, indicating distinct evolutionary adaptations at the mRNA level.
• Tissue-specific expression patterns of RAGE variants suggest specialized functional roles in different developmental stages and physiological contexts.