---
title: "AltORF-encoded microprotein GndA recruits Gnd dehydrogenase to poles during heat shock"
id: "biorxiv-12-altorf-encoded-microprotein-recruits-primary-orf-encoded-dehydrogenase-to-cell"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-12-altorf-encoded-microprotein-recruits-primary-orf-encoded-dehydrogenase-to-cell"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.22.760973v1?rss=1"
published_at: "2026-10-25T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# AltORF-encoded microprotein GndA recruits Gnd dehydrogenase to poles during heat shock
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-12-altorf-encoded-microprotein-recruits-primary-orf-encoded-dehydrogenase-to-cell
- **Specialty:** [General](https://medichelpline.com/clinical-feed/general.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.22.760973v1?rss=1)
- **Published At:** 2026-10-25T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The authors characterized an altORF within the E. coli gnd gene that encodes a microprotein they named **GndA**. The study focused on expression, regulation, localization, and functional effects of this microprotein during heat shock. - Data indicated **GndA** is induced by heat shock but is unstable, whereas the canonical **Gnd** 6-phosphogluconate dehydrogenase protein remains stable with unchanged steady-state levels under the same conditions. - Translational fusion assays and in vivo RNA structure probing were used by the study team to map a thermo-responsive RNA element upstream of gndA; an internal complementary sequence forms a secondary structure that the authors reported controls GndA translation in a temperature-dependent manner. - Mutagenesis of either gnd or gndA reduced heat shock survival of E. coli in the experiments, indicating both the primary ORF product (**Gnd**) and the altORF product (**GndA**) contribute to resistance. - Biochemical fractionation showed **GndA** partitioned with membranes, consistent with computational predictions that it forms an amphipathic α-helix, while **Gnd** was predominantly cytoplasmic in unstressed cells. - The authors observed **Gnd** relocalization to cell poles upon heat shock, and they reported that this stress-dependent polar relocalization required **GndA**, implicating a functional interplay between overlapping ORF-encoded proteins during stress adaptation. - The source did not report detailed kinetics of GndA turnover, exact sequence of the complementary region, or quantitative proteomics metrics beyond the qualitative observations described in the abstract and main text provided.
## Clinical Analysis & Structured Key Points
AltORF-encoded microprotein recruits primary-ORF-encoded dehydrogenase to cell poles upon heat shock | bioRxiv Skip to main content New Results AltORF-encoded microprotein recruits primary-ORF-encoded dehydrogenase to cell poles upon heat shock View ORCID Profile Janka J. Schmidt , View ORCID Profile Felix Ramos-Leon , Aixia Zhang , View ORCID Profile Rilee Zeinert , View ORCID Profile Svetlana A. Shabalina , View ORCID Profile Gisela Storz doi: https://doi.org/10.64898/2026.10.22.760973 Janka J. Schmidt 1 National Institute of Child Health and Human Development, NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Janka J. Schmidt Felix Ramos-Leon 2 National Cancer Institute; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Felix Ramos-Leon Aixia Zhang 1 National Institute of Child Health and Human Development, NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Rilee Zeinert 1 National Institute of Child Health and Human Development, NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Rilee Zeinert Svetlana A. Shabalina 3 National Library of Medicine; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Svetlana A. Shabalina Gisela Storz 4 NICHD, NIH Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Gisela Storz For correspondence: storzg{at}mail.nih.gov Abstract Info/History Metrics Supplementary material Preview PDF Abstract Alternative open reading frames (altORFs) initiating from in-frame or out-of-frame start sites within annotated protein-coding genes represent a largely unexplored source of protein-coding potential and remain poorly understood in terms of regulation, function, and impact on physiology. Here we investigate Escherichia coli GndA, encoded by an out-of-frame altORF within gnd, which encodes 6-phosphogluconate dehydrogenase. We observe that the GndA protein is induced by heat shock, consistent with the initial identification in a quantitative membrane proteomics screen, but is unstable, while the levels of the stable Gnd dehydrogenase are unchanged. Using translational fusion assays and in vivo RNA structure probing, we show that an internal complementary sequence upstream of gndA acts as a thermo-responsive secondary RNA structure controlling GndA translation. Mutagenesis of either gnd or gndA reduce heat shock survival of E. coli indicating both gene products are important for resistance. GndA fractionates with membranes consistent with in silico predictions that the protein forms an amphipathic α-helix. In contrast, Gnd is predominantly cytoplasmic but shows GndA-dependent relocalization to cell poles upon heat shock. Together, our results demonstrate that an altORF-encoded microprotein is required for stress-dependent relocalization of its primary ORF partner, revealing a functional interplay between proteins encoded by overlapping ORFs in bacterial stress adaptation. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared Eunice Kennedy Shriver National Institute of Child Health and Human Development, https://ror.org/04byxyr05 , HD001608 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. Back to top Previous Next Posted October 25, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following AltORF-encoded microprotein recruits primary-ORF-encoded dehydrogenase to cell poles upon heat shock Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share AltORF-encoded microprotein recruits primary-ORF-encoded dehydrogenase to cell poles upon heat shock Janka J. Schmidt , Felix Ramos-Leon , Aixia Zhang , Rilee Zeinert , Svetlana A. Shabalina , Gisela Storz bioRxiv 2026.10.22.760973; doi: https://doi.org/10.64898/2026.10.22.760973 Share This Article: Copy Citation Tools AltORF-encoded microprotein recruits primary-ORF-encoded dehydrogenase to cell poles upon heat shock Janka J. Schmidt , Felix Ramos-Leon , Aixia Zhang , Rilee Zeinert , Svetlana A. Shabalina , Gisela Storz bioRxiv 2026.10.22.760973; doi: https://doi.org/10.64898/2026.10.22.760973 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Microbiology Subject Areas All Articles Animal Behavior and Cognition (8164) Biochemistry (19027) Bioengineering (15171) Bioinformatics (45372) Biophysics (22958) Cancer Biology (20120) Cell Biology (27314) Clinical Trials (138) Developmental Biology (14149) Ecology (21402) Epidemiology (2067) Evolutionary Biology (25816) Genetics (16349) Genomics (23848) Immunology (19033) Microbiology (43209) Molecular Biology (18346) Neuroscience (95152) Paleontology (714) Pathology (3036) Pharmacology and Toxicology (5201) Physiology (8287) Plant Biology (16274) Scientific Communication and Education (2116) Synthetic Biology (4647) Systems Biology (10389) Zoology (2427)
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