2. Academic Validation
  3. RNA Polymerases I and III in development and disease

RNA Polymerases I and III in development and disease

  • Semin Cell Dev Biol. 2023 Feb 28:136:49-63. doi: 10.1016/j.semcdb.2022.03.027.
Kristin En Watt 1,  Julia Macintosh 2,  Geneviève Bernard 3,  Paul A Trainor 4
Affiliations

Affiliations

  • 1 Stowers Institute for Medical Research, Kansas City, MO, USA.
  • 2 Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada; Child Health and Human Development Program, Research Institute of the McGill University Health Center, Montreal, QC, Canada.
  • 3 Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada; Child Health and Human Development Program, Research Institute of the McGill University Health Center, Montreal, QC, Canada; Departments of Pediatrics and Human Genetics, McGill University, Montreal, QC, Canada; Department of Specialized Medicine, Division of Medical Genetics, McGill University Health Center, Montreal, QC, Canada. Electronic address: [email protected].
  • 4 Stowers Institute for Medical Research, Kansas City, MO, USA; Department of Anatomy & Cell Biology, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: [email protected].
PMID: 35422389 DOI: 10.1016/j.semcdb.2022.03.027
Abstract

Ribosomes are macromolecular machines that are globally required for the translation of all proteins in all cells. Ribosome biogenesis, which is essential for cell growth, proliferation and survival, commences with transcription of a variety of RNAs by RNA Polymerases I and III. RNA Polymerase I (Pol I) transcribes ribosomal RNA (rRNA), while RNA Polymerase III (Pol III) transcribes 5S ribosomal RNA and transfer RNAs (tRNA) in addition to a wide variety of small non-coding RNAs. Interestingly, despite their global importance, disruptions in Pol I and Pol III function result in tissue-specific developmental disorders, with craniofacial anomalies and leukodystrophy/neurodegenerative disease being among the most prevalent. Furthermore, pathogenic variants in genes encoding subunits shared between Pol I and Pol III give rise to distinct syndromes depending on whether Pol I or Pol III function is disrupted. In this review, we discuss the global roles of Pol I and III transcription, the consequences of disruptions in Pol I and III transcription, disorders arising from pathogenic variants in Pol I and Pol III subunits, and mechanisms underpinning their tissue-specific phenotypes.

Keywords

POLR3-related leukodystrophy; RNA Polymerase I; RNA Polymerase III; Ribosome biogenesis; Treacher Collins syndrome; rRNA.

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