Insertion of 29 Bases Derived From an Intron Leads to the Polymorphism of Ufc1 in Rodent Species

抄録

A Ufc1 polymorphism known as “Ufc1 short-form” has been identified in rat brains. The properties of this mRNA products have not been fully analyzed. In this study, we perform an analysis of the mRNA and its predicted translation product using various in silico methods. The key findings are as follows: (1) The Ufc1 short-form mRNA (GenBank Accession: AB441169.1) in rat brains contains a 29-base insertion in the conventional Ufc1 open reading frame, which leads to the encoding of 93 amino acids due to a novel stop codon present in an intron retention. (2) Ufc1 short-form lacks the Ufm1-binding region, which may have deleterious effects on the Ufm1 system. (3) Ufc1 short-form has a C-terminal sequence (-EWEV) that corresponds to the peptide sequence recognized by the PSD-95/Dlg/ZO-1 (PDZ) domain. Relative to the long-form (i.e., conventional Ufc1), the short-form is predicted to have a higher affinity for glutamate receptor-interacting protein 1 (GRIP1) and calcium/calmodulin-dependent serine protein kinase (CASK) in neurons via PDZ domain-binding. This prediction suggests the potential disruption of normal neuronal protein structures. The insertion of 29 bases results in the generation of splicing variants in rodent Ufc1, indicating that this may lead to functional diversity of Ufc1 and potentially impact the Ufm1 system and associated pathways.