8.A.185.1.7
SLC35A4-MP (microprotein) of 103 aas and 1 TMS.  It is an inner mitochondrial membrane microprotein from the SLC35A4 upstream ORF, and it regulates cellular metabolism (Rocha et al. 2024).  Upstream ORFs (uORFs) are cis-acting elements that can regulate the translation of downstream ORFs by suppressing downstream translation under basal conditions and, in some cases, increasing downstream translation under stress conditions. Methods have identified uORFs in the 5'-UTRs of approximately half of all mouse and human transcripts. Because the prevailing dogma was that eukaryotic mRNAs produce a single functional protein, the peptides or microproteins, encoded by uORFs were rarely studied. We hypothesized that a uORF in the SLC35A4 mRNA is producing a functional microprotein (SLC35A4-MP) because of its conserved amino acid sequence. The IMM contains the protein machinery crucial for cellular respiration and ATP generation, and loss of function studies with SLC35A4-MP significantly diminish maximal cellular respiration, indicating a vital role for this microprotein in cellular metabolism. The findings add SLC35A4-MP to the growing list of functional microproteins (Rocha et al. 2024).