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Cryo-EM structures of human RNA polymerase I.

Misiaszek AD, Girbig M, Grötsch H, Baudin F, Murciano B, Lafita A, Müller CW
Nat Struct Mol Biol 28 997-1008 (2021)
Related entries: 7ob9, 7obb

Cited: 23 times
EuropePMC logo PMID: 34887565

Abstract

RNA polymerase I (Pol I) specifically synthesizes ribosomal RNA. Pol I upregulation is linked to cancer, while mutations in the Pol I machinery lead to developmental disorders. Here we report the cryo-EM structure of elongating human Pol I at 2.7 Å resolution. In the exit tunnel, we observe a double-stranded RNA helix that may support Pol I processivity. Our structure confirms that human Pol I consists of 13 subunits with only one subunit forming the Pol I stalk. Additionally, the structure of human Pol I in complex with the initiation factor RRN3 at 3.1 Å resolution reveals stalk flipping upon RRN3 binding. We also observe an inactivated state of human Pol I bound to an open DNA scaffold at 3.3 Å resolution. Lastly, the high-resolution structure of human Pol I allows mapping of disease-related mutations that can aid understanding of disease etiology.

Reviews - 7oba mentioned but not cited (2)

  1. Ribosome biogenesis factors-from names to functions. Dörner K, Ruggeri C, Zemp I, Kutay U. EMBO J 42 e112699 (2023)
  2. Regulation of RNA Polymerase I Stability and Function. Pitts S, Laiho M. Cancers (Basel) 14 5776 (2022)

Articles - 7oba mentioned but not cited (2)

  1. Cryo-EM structures of human RNA polymerase I. Misiaszek AD, Girbig M, Grötsch H, Baudin F, Murciano B, Lafita A, Müller CW. Nat Struct Mol Biol 28 997-1008 (2021)
  2. Current status and future perspectives of the evaluation of missense variants by using three-dimensional structures of proteins. Shirota M, Kinoshita K. Biophys Physicobiol 19 e190023 (2022)


Reviews citing this publication (7)

  1. Targeting Ribosome Biogenesis in Cancer: Lessons Learned and Way Forward. Zisi A, Bartek J, Lindström MS. Cancers (Basel) 14 2126 (2022)
  2. Structural insights into nuclear transcription by eukaryotic DNA-dependent RNA polymerases. Girbig M, Misiaszek AD, Müller CW. Nat Rev Mol Cell Biol 23 603-622 (2022)
  3. 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)
  4. 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)
  5. Development of Single Molecule Techniques for Sensing and Manipulation of CRISPR and Polymerase Enzymes. Chu J, Romero A, Taulbee J, Aran K. Small 19 e2300328 (2023)
  6. Embracing Heterogeneity: Challenging the Paradigm of Replisomes as Deterministic Machines. Lewis JS, van Oijen AM, Spenkelink LM. Chem Rev 123 13419-13440 (2023)
  7. Polymerase I as a Target for Treating Neurodegenerative Disorders. LeDoux MS. Biomedicines 12 1092 (2024)

Articles citing this publication (12)

  1. Dynamic regulation and requirement for ribosomal RNA transcription during mammalian development. Falcon KT, Watt KEN, Dash S, Zhao R, Sakai D, Moore EL, Fitriasari S, Childers M, Sardiu ME, Swanson S, Tsuchiya D, Unruh J, Bugarinovic G, Li L, Shiang R, Achilleos A, Dixon J, Dixon MJ, Trainor PA. Proc Natl Acad Sci U S A 119 e2116974119 (2022)
  2. An integrated model for termination of RNA polymerase III transcription. Xie J, Aiello U, Clement Y, Haidara N, Girbig M, Schmitzova J, Pena V, Müller CW, Libri D, Porrua O. Sci Adv 8 eabm9875 (2022)
  3. 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)
  4. Identification of an E3 ligase that targets the catalytic subunit of RNA Polymerase I upon transcription stress. Pitts S, Liu H, Ibrahim A, Garg A, Felgueira CM, Begum A, Fan W, Teh S, Low JY, Ford B, Schneider DA, Hay R, Laiho M. J Biol Chem 298 102690 (2022)
  5. POLR1A variants underlie phenotypic heterogeneity in craniofacial, neural, and cardiac anomalies. Smallwood K, Watt KEN, Ide S, Baltrunaite K, Brunswick C, Inskeep K, Capannari C, Adam MP, Begtrup A, Bertola DR, Demmer L, Demo E, Devinsky O, Gallagher ER, Guillen Sacoto MJ, Jech R, Keren B, Kussmann J, Ladda R, Lansdon LA, Lunke S, Mardy A, McWalters K, Person R, Raiti L, Saitoh N, Saunders CJ, Schnur R, Skorvanek M, Sell SL, Slavotinek A, Sullivan BR, Stark Z, Symonds JD, Wenger T, Weber S, Whalen S, White SM, Winkelmann J, Zech M, Zeidler S, Maeshima K, Stottmann RW, Trainor PA, Weaver KN. Am J Hum Genet 110 809-825 (2023)
  6. 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)
  7. rRNA transcription is integral to phase separation and maintenance of nucleolar structure. Dash S, Lamb MC, Lange JJ, McKinney MC, Tsuchiya D, Guo F, Zhao X, Corbin TJ, Kirkman M, Delventhal K, Moore EL, McKinney S, Shiang R, Trainor PA. PLoS Genet 19 e1010854 (2023)
  8. A structural perspective of human RNA polymerase III. Wang Q, Lei M, Wu J. RNA Biol 19 246-255 (2022)
  9. Crossing boundaries of light microscopy resolution discerns novel assemblies in the nucleolus. Correll CC, Rudloff U, Schmit JD, Ball DA, Karpova TS, Balzer E, Dundr M. Histochem Cell Biol (2024)
  10. DNA-dependent RNA polymerases in plants. Yang DL, Huang K, Deng D, Zeng Y, Wang Z, Zhang Y. Plant Cell 35 3641-3661 (2023)
  11. Distinct Interaction Modes for the Eukaryotic RNA Polymerase Alpha-like Subunits. Belkevich AE, Pascual HG, Fakhouri AM, Ball DG, Knutson BA. Mol Cell Biol 43 269-282 (2023)
  12. PAF49: An RNA Polymerase I subunit essential for rDNA transcription and stabilization of PAF53. McNamar R, Freeman E, Baylor KN, Fakhouri AM, Huang S, Knutson BA, Rothblum LI. J Biol Chem 299 104951 (2023)


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