The set of mutations we have detected in both the promoter and untranslated regions are of significant relevance in explaining the high level of variation in Per3 mRNA levels. Complex transcription regulatory loops and posttranscriptional decay mechanisms are known to modulate the normal diurnal dynamics of Per3 expression.54, 55, 56 The sequence of the 3′ UTR is important in decay kinetics of Per3 mRNA, and mutations in a U-rich stretch can radically alter message stability.54 However, none of the 3′ UTR SNPs between B and D alleles overlap this crucial U-rich region. Per3 also has long and short 3′ UTR isoforms. We therefore cannot dismiss differences in 3′ UTR structure and mRNA decay rates as a possible source of variation in Per3 message levels.
