Split genes and their expression in Kaposi's sarcoma-associated herpesvirus

Area of Science:

• Molecular Virology
• Gene Expression
• Bioinformatics

Background:

• Split genes, composed of introns and exons, necessitate RNA splicing to form mature messenger RNA (mRNA).
• Initial gene identification in the KSHV genome overlooked gene discontinuity, focusing on coding potential.
• Understanding KSHV gene structure is crucial for deciphering viral replication and pathogenesis.

Purpose of the Study:

• To identify and characterize split genes within the KSHV genome.
• To investigate the expression patterns and complexity of KSHV split genes.
• To explore the implications of alternative splicing in KSHV gene expression.

Main Methods:

• Bioinformatic analysis of the KSHV genome to identify potential split genes.
• Experimental validation of predicted split genes and their transcripts.
• Analysis of gene expression, including promoter and polyadenylation signal usage.
• Investigation of alternative splicing events in specific KSHV genes.

Main Results:

• Up to 25 split genes (over 25% of KSHV genes) were identified, impacting all infection phases.
• Many KSHV split genes share promoters or polyadenylation signals, leading to polycistronic transcripts (15 bicistronic/tricistronic, 10 monocistronic).
• Alternative RNA splicing generates transcript diversity, with K8 and K15 producing at least 8 and 14 species, respectively.

Conclusions:

• KSHV possesses a significant number of split genes, adding complexity to its gene expression.
• Polycistronic transcription and alternative splicing are key mechanisms in KSHV gene regulation.
• These complex splicing events are likely linked to cell differentiation and KSHV infection stages.