CSN1S1 and CSN1S2: Two Remarkable Examples of Genetically Modulated Alternative Splicing via Identification of...

Area of Science:

• Molecular Biology
• Genetics
• Animal Science

Background:

• Splicing regulatory sequences are crucial for accurate mRNA maturation and protein synthesis.
• Mutations in these sequences, including SNPs and InDels, can disrupt gene expression by altering splice sites or creating cryptic ones.
• The CSN1S1 and CSN1S2 genes, encoding key milk proteins (caseins), exhibit extensive alternative splicing and allele-specific events.

Purpose of the Study:

• To review the impact of mutations affecting canonical splice sites on casein gene expression in major dairy livestock.
• To highlight the genetic variation introduced by these mutations and their consequences on milk protein production.
• To identify current limitations and suggest future research directions for understanding casein splicing.

Main Methods:

• Literature review of studies on CSN1S1 and CSN1S2 gene splicing.
• Analysis of reported mutations affecting splice sites in various livestock species (Bos taurus, Ovis aries, Capra hircus, Bubalus bubalis, Camelidae, Equus asinus).
• Identification of allele-specific splicing events linked to these mutations.

Main Results:

• At least 13 alleles of CSN1S1 and several alleles of CSN1S2 are associated with mutations in canonical splice sites across different species.
• Mutations, especially in donor splice sites, are significant drivers of genetic variation impacting casein production.
• Allele-specific splicing events are well-documented in both CSN1S1 and CSN1S2 loci.

Conclusions:

• Mutations impacting canonical splice sites are a major source of genetic variation affecting casein production in dairy animals.
• A significant knowledge gap exists regarding detailed functional and proteomic studies of these splicing alterations.
• Advanced omics technologies, such as long-read transcriptomics and allele-resolved RNA sequencing, are recommended for future research to guide precision breeding.