STREMI: A Dual-Function Upstream ORF-Encoded Regulator of Mitochondrial Cristae Architecture

ABSTRACT: Eukaryotic mRNAs typically encode a single functional polypeptide, a principle challenged by the discovery of widespread non-canonical peptide-coding ORFs within 5'UTRs. However, their functional significance at the protein level remains underexplored. Using a four-layered pipeline, we identify 14 human transcripts predominantly transcribed in polycistronic forms, each encoding two conserved proteins. Focusing on the SLC35A4 transcript, we show that its 5'UTR encodes a mitochondrial inner membrane-localized microprotein that we name STREMI (SLC35A4 stress response regulating MICOS interactor). Sharing topology and motifs with the MICOS core subunit MIC10, STREMI regulates mitochondrial cristae morphogenesis in mice and human cells. Additionally, the STREMI-encoding uORF mediates stress-res

SUBMITTER: Ruiyang Guo 

PROVIDER: S-SCDT-10_1038-S44319-026-00783-8 | biostudies-other |

REPOSITORIES: biostudies-other