Possible utilization of -1 Ribosomal frame shifting in the expression of a human SEMA6C isoform

We have used bioinformatics approaches to identify a potential case of -1 ribosomal frame shifting in the mRNAs of the three variants of human SEMA6C protein. The mRNAs contain a heptanucleotide slippery sequence followed by a compact H-type pseudoknot. Unlike -1 frameshifting signals in viral or viral-like mRNAs, the slippery sequence and downstream pseudoknot in SEMA6C mRNAs locate 423 nucleotides (encoding 141 amino acids) upstream of the stop codon. The potential -1 frameshifting event would produce a polypeptide of 238 residues encoded by the -1 reading frames. Sequence similarity searches using BLAST indicate that ~90% of the 238 residues match actual protein sequences annotated as SEMA6C proteins in the database. We propose that the mRNAs of human SEMA6C utilize a pseudoknot dependent -1 ribosomal frameshifting mechanism to express novel SEMA6C isoforms.