Expression and regulation of mouse selenoprotein P transcript variants differing in non-coding RNA

Area of Science:

• Molecular Biology
• Genetics
• Neuroscience

Background:

• Selenoprotein P (Sepp1) is a selenium-rich glycoprotein involved in selenium transport.
• Genomic databases suggest the Sepp1 gene locus produces three alternative transcripts with distinct 5' untranslated regions (5'UTRs).

Purpose of the Study:

• To investigate the distribution, relative expression, and biological significance of Sepp1 transcript variants.
• To explore the regulatory mechanisms and functional implications of these variants, particularly in the brain.

Main Methods:

• RT-PCR and sequencing to confirm transcript variant expression.
• 5'-RACE to identify transcript 5'-termini.
• RNA interference (RNAi) for targeted variant silencing.
• Bioinformatic analysis to identify microRNA targets.

Main Results:

• Expression of Sepp1 transcript variants was confirmed, with regional and temporal variations observed in murine tissues and brain regions.
• The Sepp1b variant was specifically localized to the hippocampus.
• Targeted silencing of individual variants demonstrated their importance for cell viability.
• The Sepp1b variant was identified as a target of miR-7 microRNA due to its unique 5'UTR structure.

Conclusions:

• Non-coding transcript variations in Sepp1 play a significant regulatory role in different tissues and developmental stages.
• The hippocampus-specific Sepp1b variant, regulated by miR-7, may be relevant to synaptic function deficits observed in Sepp1 knockout models.