Translation of an upstream open reading frame (uORF) can negatively affect translation of the primary protein-coding open reading frame (pORF) (31). This effect does not always completely silence pORF translation and may be dependent on cell type, developmental state or cellular condition. Therefore, although uORFs may be predicted from the six-frame translation of a transcript, the regulatory effect of this element must be determined through experimental validation. RefSeq curators reviewed the literature to find transcripts with experimental evidence of regulatory uORFs and updated the corresponding RefSeq transcript records to add a misc_feature denoting the location of these uORFs. An example is the RefSeq entry NM_000392.4 for ABCC2 (GeneID: 1244). A new RefSeq attribute category entitled ‘regulatory uORF’ was created and appears in a structured comment on these RefSeq records. Both the annotated feature and the attribute cite the supporting publication by PubMed ID. To date, 260 records have been annotated with this attribute and these records can be retrieved from the Nucleotide database by searching for ‘regulatory uORF [properties]’
