ArticleNucleic acids research2018
Crystal structure of dimeric human PNPase reveals why disease-linked mutants suffer from low RNA import and degradation activities.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
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- Mitochondrial genome microhomology-mediated editing by donor DNA delivery into mitochondria in human cells.Molecular therapy. Nucleic acids · 2026Article
- Feedforward miR-181d degradation modulates population variance of methyl-guanine methyl transferase and temozolomide resistance.Cell reports · 2025Article
- Human polynucleotide phosphorylase in mitochondrial RNA metabolism.Bioscience reports · 2025Review
- Mechanisms of microRNA trafficking to mitochondria in the heart.Current opinion in physiology · 2025Article
- Targeted deletions in human mitochondrial DNA engineered by Type V CRISPR-Cas12a system.NAR molecular medicine · 2025Article
- Structural insights into human PNPase in health and disease.Nucleic acids research · 2025Article
- Pathological PNPase variants with altered RNA binding and degradation activity affect the phenotype of bacterial and human cell models.NAR molecular medicine · 2025Article
- Mitochondrial sequencing identifies long noncoding RNA features that promote binding to PNPase.American journal of physiology. Cell physiology · 2024Article
- How RNases Shape Mitochondrial Transcriptomes.International journal of molecular sciences · 2022Review
- Activity and Function in Human Cells of the Evolutionary Conserved Exonuclease Polynucleotide Phosphorylase.International journal of molecular sciences · 2022Review
- Current perspectives on the clinical implications of oxidative RNA damage in aging research: challenges and opportunities.GeroScience · 2021Review
- Clinical Spectrum and Functional Consequences Associated with Bi-Allelic PathogenicJournal of clinical medicine · 2019Article
- Structural insights into nanoRNA degradation by human Rexo2.RNA (New York, N.Y.) · 2019Article
- Import of Non-Coding RNAs into Human Mitochondria: A Critical Review and Emerging Approaches.Cells · 2019Review
- Spatiotemporal Control of microRNA-Target Interactions.Wiley interdisciplinary reviews. RNAReview
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human polynucleotide phosphorylase (PNPase) is an evolutionarily conserved 3'-to-5' exoribonuclease principally located in mitochondria where it is responsible for RNA turnover and import. Mutations in PNPase impair structured RNA transport into mitochondria, resulting in mitochondrial dysfunction and disease. PNPase is a trimeric protein with a doughnut-shaped structure hosting a central channel for single-stranded RNA binding and degradation. Here, we show that the disease-linked human PNPase mutants, Q387R and E475G, form dimers, not trimers, and have significantly lower RNA binding and degradation activities compared to wild-type trimeric PNPase. Moreover, S1 domain-truncated PNPase binds single-stranded RNA but not the stem-loop signature motif of imported structured RNA, suggesting that the S1 domain is responsible for binding structured RNAs. We further determined the crystal structure of dimeric PNPase at a resolution of 2.8 Å and, combined with small-angle X-ray scattering, show that the RNA-binding K homology and S1 domains are relatively inaccessible in the dimeric assembly. Taken together, these results show that mutations at the interface of the trimeric PNPase tend to produce a dimeric protein with destructive RNA-binding surfaces, thus impairing both of its RNA import and degradation activities and leading to mitochondria disorders.
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