By convention, a genetic variant in the DNA sequence that occurs in a population with a frequency of 1% or higher is defined as “polymorphism” while the rarer ones (frequency <1%) are defined as “mutations”.13,14 Polymorphisms and mutations can comprise one or more nucleotide changes. Interestingly, mutations predominate in 5′UTRs, while polymorphisms are more common in 3′UTRs.13,14 Gene expression is regulated at the RNA level by virtue of the presence of 5′ and 3′UTR regulatory elements such as upstream open reading frames (uORFs), internal ribosome entry sites (IRESs), as well as the UTR’s secondary structure, sequence composition, and length. The majority of regulatory elements are recognized by RBPs or by non-coding RNAs (ncRNAs) such as miRNAs. Overall, these mechanisms modulate the mRNA stability, localization, and translation.15,16
