7ast › Citations

Structure of human RNA polymerase III.

<div class='caption-title'>Purification of GFP-tagged endogenous human RNA polymerase III.</div>
<div class='caption-title'>The structure of human RNA polymerase III.</div>
<div class='caption-title'>Structure of the RPC5 subunit C-terminal region.</div>
Ramsay EP, Abascal-Palacios G, Daiß JL, King H, Gouge J, Pilsl M, Beuron F, Morris E, Gunkel P, Engel C, Vannini A
OpenAccess logo Nat Commun 11 6409 (2020)
Related entries: 7asu, 7asv

Cited: 33 times
EuropePMC logo PMID: 33335104

Abstract

In eukaryotes, RNA Polymerase (Pol) III is specialized for the transcription of tRNAs and other short, untranslated RNAs. Pol III is a determinant of cellular growth and lifespan across eukaryotes. Upregulation of Pol III transcription is observed in cancer and causative Pol III mutations have been described in neurodevelopmental disorders and hypersensitivity to viral infection. Here, we report a cryo-EM reconstruction at 4.0 Å of human Pol III, allowing mapping and rationalization of reported genetic mutations. Mutations causing neurodevelopmental defects cluster in hotspots affecting Pol III stability and/or biogenesis, whereas mutations affecting viral sensing are located in proximity to DNA binding regions, suggesting an impairment of Pol III cytosolic viral DNA-sensing. Integrating x-ray crystallography and SAXS, we also describe the structure of the higher eukaryote specific RPC5 C-terminal extension. Surprisingly, experiments in living cells highlight a role for this module in the assembly and stability of human Pol III.

Articles - 7ast mentioned but not cited (1)

  1. The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans. Daiß JL, Pilsl M, Straub K, Bleckmann A, Höcherl M, Heiss FB, Abascal-Palacios G, Ramsay EP, Tlučková K, Mars JC, Fürtges T, Bruckmann A, Rudack T, Bernecky C, Lamour V, Panov K, Vannini A, Moss T, Engel C. Life Sci Alliance 5 e202201568 (2022)


Reviews citing this publication (12)

  1. Battle Royale: Innate Recognition of Poxviruses and Viral Immune Evasion. Yu H, Bruneau RC, Brennan G, Rothenburg S. Biomedicines 9 765 (2021)
  2. RNA Polymerase III Subunit Mutations in Genetic Diseases. Lata E, Choquet K, Sagliocco F, Brais B, Bernard G, Teichmann M. Front Mol Biosci 8 696438 (2021)
  3. Regulation of Eukaryotic RNAPs Activities by Phosphorylation. González-Jiménez A, Campos A, Navarro F, Clemente-Blanco A, Calvo O. Front Mol Biosci 8 681865 (2021)
  4. Regulation of ribosomal RNA gene copy number, transcription and nucleolus organization in eukaryotes. Hori Y, Engel C, Kobayashi T. Nat Rev Mol Cell Biol 24 414-429 (2023)
  5. Specific Features of RNA Polymerases I and III: Structure and Assembly. Turowski TW, Boguta M. Front Mol Biosci 8 680090 (2021)
  6. tRNA dysregulation and disease. Orellana EA, Siegal E, Gregory RI. Nat Rev Genet 23 651-664 (2022)
  7. Molecular Pathogenic Mechanisms of Hypomyelinating Leukodystrophies (HLDs). Torii T, Yamauchi J. Neurol Int 15 1155-1173 (2023)
  8. RNA Polymerases I and III in development and disease. Watt KE, Macintosh J, Bernard G, Trainor PA. Semin Cell Dev Biol 136 49-63 (2023)
  9. RNA polymerase III transcription and cancer: A tale of two RPC7 subunits. Cheng R, Van Bortle K. Front Mol Biosci 9 1073795 (2022)
  10. Structural Studies of Eukaryotic RNA Polymerase I Using Cryo-Electron Microscopy. Pilsl M, Engel C. Methods Mol Biol 2533 71-80 (2022)
  11. Structural insights into nuclear transcription by eukaryotic DNA-dependent RNA polymerases. Girbig M, Misiaszek AD, Müller CW. Nat Rev Mol Cell Biol (2022)
  12. The RNA polymerase III-RIG-I axis in antiviral immunity and inflammation. Naesens L, Haerynck F, Gack MU. Trends Immunol 44 435-449 (2023)

Articles citing this publication (20)

  1. Mechanism of RNA polymerase III termination-associated reinitiation-recycling conferred by the essential function of the N terminal-and-linker domain of the C11 subunit. Mishra S, Hasan SH, Sakhawala RM, Chaudhry S, Maraia RJ. Nat Commun 12 5900 (2021)
  2. DNA Intercalators Inhibit Eukaryotic Ribosomal RNA Synthesis by Impairing the Initiation of Transcription. Andrews WJ, Ray S, Panova T, Engel C, Panov KI. Genes (Basel) 12 1412 (2021)
  3. Defective myelination in an RNA polymerase III mutant leukodystrophic mouse. Merheb E, Cui MH, DuBois JC, Branch CA, Gulinello M, Shafit-Zagardo B, Moir RD, Willis IM. Proc Natl Acad Sci U S A 118 e2024378118 (2021)
  4. POLR3-Related Leukodystrophy: Exploring Potential Therapeutic Approaches. Perrier S, Michell-Robinson MA, Bernard G. Front Cell Neurosci 14 631802 (2020)
  5. RNA Polymerase I Is Uniquely Vulnerable to the Small-Molecule Inhibitor BMH-21. Jacobs RQ, Fuller KB, Cooper SL, Carter ZI, Laiho M, Lucius AL, Schneider DA. Cancers (Basel) 14 5544 (2022)
  6. How can same-gene mutations promote both cancer and developmental disorders? Nussinov R, Tsai CJ, Jang H. Sci Adv 8 eabm2059 (2022)
  7. Structural insights into RNA polymerase III-mediated transcription termination through trapping poly-deoxythymidine. Hou H, Li Y, Wang M, Liu A, Yu Z, Chen K, Zhao D, Xu Y. Nat Commun 12 6135 (2021)
  8. The nuclear and cytoplasmic activities of RNA polymerase III, and an evolving transcriptome for surveillance. Kessler AC, Maraia RJ. Nucleic Acids Res 49 12017-12034 (2021)
  9. A Combinatorial Regulatory Platform Determines Expression of RNA Polymerase III Subunit RPC7α (POLR3G) in Cancer. Cheng R, Zhou S, K C R, Lizarazo S, Mouli L, Jayanth A, Liu Q, Van Bortle K. Cancers (Basel) 15 4995 (2023)
  10. A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA. Van Bortle K, Marciano DP, Liu Q, Chou T, Lipchik AM, Gollapudi S, Geller BS, Monte E, Kamakaka RT, Snyder MP. Nat Commun 13 3007 (2022)
  11. A structural perspective of human RNA polymerase III. Wang Q, Lei M, Wu J. RNA Biol 19 246-255 (2022)
  12. Case Reports Biallelic pathogenic variants in POLR3D alter tRNA transcription and cause a hypomyelinating leukodystrophy: A case report. Macintosh J, Perrier S, Pinard M, Tran LT, Guerrero K, Prasad C, Prasad AN, Pastinen T, Thiffault I, Coulombe B, Bernard G. Front Neurol 14 1254140 (2023)
  13. CRISPR screening reveals a dependency on ribosome recycling for efficient SARS-CoV-2 programmed ribosomal frameshifting and viral replication. Rehfeld F, Eitson JL, Ohlson MB, Chang TC, Schoggins JW, Mendell JT. Cell Rep 42 112076 (2023)
  14. Decreased RNA polymerase III subunit expression leads to defects in oligodendrocyte development. Macintosh J, Michell-Robinson M, Chen X, Bernard G. Front Neurosci 17 1167047 (2023)
  15. Evolution of the RNA Cleavage Subunit C11/RPC10, and Recycling by RNA Polymerase III. Mishra S, Maraia RJ. J Cell Immunol 4 65-71 (2022)
  16. Reprogramming mRNA Expression in Response to Defect in RNA Polymerase III Assembly in the Yeast Saccharomyces cerevisiae. Rudzińska I, Cieśla M, Turowski TW, Armatowska A, Leśniewska E, Boguta M. Int J Mol Sci 22 7298 (2021)
  17. Riluzole partially restores RNA polymerase III complex assembly in cells expressing the leukodystrophy-causative variant POLR3B R103H. Pinard M, Dastpeyman S, Poitras C, Bernard G, Gauthier MS, Coulombe B. Mol Brain 15 98 (2022)
  18. Searching for New Z-DNA/Z-RNA Binding Proteins Based on Structural Similarity to Experimentally Validated Zα Domain. Bartas M, Slychko K, Brázda V, Červeň J, Beaudoin CA, Blundell TL, Pečinka P. Int J Mol Sci 23 768 (2022)
  19. Transcriptional factor III A promotes colorectal cancer progression by upregulating cystatin A. Wang J, Tan Y, Jia QY, Tang FQ. World J Gastrointest Oncol 14 1918-1932 (2022)
  20. Transcriptional response to VZV infection is modulated by RNA polymerase III in lung epithelial cell lines. Doratt BM, Vance E, Malherbe DC, Ebbert MTW, Messaoudi I. Front Cell Infect Microbiol 12 943587 (2022)


Quick links