ArticleJournal of molecular biology2024
An Inner Mitochondrial Membrane Microprotein from the SLC35A4 Upstream ORF Regulates Cellular Metabolism.
Article in Journal of molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Local translation couples synaptic activity to mitochondrial adaptation in dendrites.bioRxiv : the preprint server for biology · 2026Article
- Ribo-ITP enables identification of translons from limited input samples.Nature communications · 2026Article
- A microprotein encoded by FERMT3 modulates endothelial cell protein catabolism and induces cell cycle arrest and senescence.Cell communication and signaling : CCS · 2026Article
- STREMI: a dual-function upstream ORF-encoded regulator of mitochondrial cristae architecture.EMBO reports · 2026Article
- Microproteins in Human Physiology and Pathology.Biochemistry · 2026Review
- Microproteins: Uncovering Hidden Layers of the Proteome.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Abnormal mitochondrial structure and function in brown adipose tissue of SLC35A4-MP knockout mice.Science advances · 2025Article
- CRISPR-Cas9 screening reveals microproteins regulating adipocyte proliferation and lipid metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mechanistic insights into Nipah virus 5' UTR functionality reveal an antiviral target.The Journal of general virology · 2025Article
- Cellular function of the GndA microprotein during heat shock.bioRxiv : the preprint server for biology · 2025Article
- The dual-coding gene SLC35A4 protects against oxidative stress.Protein science : a publication of the Protein Society · 2025Article
- Microproteins in Metabolism.Cells · 2025Review
- Early Onset Memory Deficit of WMI Rats Compared to Their Nearly Isogenic WLIs Is Reversed by Enriched Environment in Females.Genes, brain, and behavior · 2025Article
- Eukaryotic Microproteins.Annual review of biochemistry · 2025Review
- Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance.Molecular cancer · 2025Review
- Non-canonical ORFs-derived protein products in mitochondria: A multifaceted exploration of their functions in health and disease.Protein science : a publication of the Protein Society · 2025Review
- Selection Increases Mitonuclear DNA Discordance but Reconciles Incompatibility in African Cattle.Molecular biology and evolution · 2025Article
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Authors and funding
11 authors.
Funding
Abstract
Upstream open reading frames (uORFs) are cis-acting elements that can dynamically regulate the translation of downstream ORFs by suppressing downstream translation under basal conditions and, in some cases, increasing downstream translation under stress conditions. Computational and empirical methods have identified uORFs in the 5'-UTRs of approximately half of all mouse and human transcripts, making uORFs one of the largest regulatory elements known. Because the prevailing dogma was that eukaryotic mRNAs produce a single functional protein, the peptides and small proteins, 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. Through a series of biochemical and cellular experiments, we find that the 103-amino acid SLC35A4-MP is a single-pass transmembrane inner mitochondrial membrane (IMM) microprotein. 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 and, more generally, indicate that uORFs that encode conserved microproteins are an untapped reservoir of functional microproteins.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.