ArticleNucleic acids research2019
The moonlighting RNA-binding activity of cytosolic serine hydroxymethyltransferase contributes to control compartmentalization of serine metabolism.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 56 citations in OpenAlex.
- Oncolytic virus hijacks GOT1 and pyrimidinosomes to fuel pyrimidine synthesis for replication in tumor cells.Tumour virus research · 2026Article
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- Tumor suppressor function of SHMT in a Drosophila RasCell death & disease · 2026Article
- Functional divergence of two soybean cytosolic serine hydroxymethyltransferases in development and defense against soybean cyst nematode.Frontiers in plant science · 2026Article
- Article
- One-carbon metabolism in cancer: moonlighting functions of metabolic enzymes and anti-tumor therapy.Cancer metastasis reviews · 2025Review
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- The molecular chaperone TRAP1 promotes translation ofRNA (New York, N.Y.) · 2025Article
- Multifaceted role of serine hydroxymethyltransferase in health and disease.Molecules and cells · 2025Review
- RNA-mediated inhibition of mitochondrial SHMT2 impairs cancer cell proliferation.Cell death discovery · 2025Article
- RNA-binding proteins as versatile metabolic regulators.npj metabolic health and disease · 2025Article
- Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer.Clinical Medicine Insights. Oncology · 2025Review
- HNRNPH1 stabilizes FLOT2 mRNA in a non-canonical m6A-dependent manner to promote malignant progression in nasopharyngeal carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- The Pivotal Role of One-Carbon Metabolism in Neoplastic Progression During the Aging Process.Biomolecules · 2024Review
- Cytosolic RNA binding of the mitochondrial TCA cycle enzyme malate dehydrogenase.RNA (New York, N.Y.) · 2024Article
- RNA-binding proteins in cardiovascular biology and disease: the beat goes on.Nature reviews. Cardiology · 2024Review
- SHMT2 Mediates Small-Molecule-Induced Alleviation of Alzheimer Pathology Via the 5'UTR-dependent ADAM10 Translation Initiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses.Nature communications · 2024Article
- Regulatory mechanisms of one-carbon metabolism enzymes.The Journal of biological chemistry · 2023Review
- The RNA-binding protein landscapes differ between mammalian organs and cultured cells.Nature communications · 2023Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enzymes of intermediary metabolism are often reported to have moonlighting functions as RNA-binding proteins and have regulatory roles beyond their primary activities. Human serine hydroxymethyltransferase (SHMT) is essential for the one-carbon metabolism, which sustains growth and proliferation in normal and tumour cells. Here, we characterize the RNA-binding function of cytosolic SHMT (SHMT1) in vitro and using cancer cell models. We show that SHMT1 controls the expression of its mitochondrial counterpart (SHMT2) by binding to the 5'untranslated region of the SHMT2 transcript (UTR2). Importantly, binding to RNA is modulated by metabolites in vitro and the formation of the SHMT1-UTR2 complex inhibits the serine cleavage activity of the SHMT1, without affecting the reverse reaction. Transfection of UTR2 in cancer cells controls SHMT1 activity and reduces cell viability. We propose a novel mechanism of SHMT regulation, which interconnects RNA and metabolites levels to control the cross-talk between cytosolic and mitochondrial compartments of serine metabolism.
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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.