Perturbations at the ribosomal genes loci are at the centre of cellular dysfunction and human disease

Jeannine Diesch; Ross D Hannan; Elaine Sanij

doi:10.1186/2045-3701-4-43

Perturbations at the ribosomal genes loci are at the centre of cellular dysfunction and human disease

Cell Biosci. 2014 Aug 19:4:43. doi: 10.1186/2045-3701-4-43. eCollection 2014.

Authors

Jeannine Diesch¹, Ross D Hannan², Elaine Sanij³

Affiliations

¹ Growth Control Laboratory, Research Division, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria 3002, Australia ; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010, Australia.
² Growth Control Laboratory, Research Division, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria 3002, Australia ; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010, Australia ; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia ; Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3010, Australia ; Division of Cancer Medicine, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria 3002, Australia ; School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia.
³ Growth Control Laboratory, Research Division, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria 3002, Australia ; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010, Australia ; Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia.

Abstract

Ribosomal RNA (rRNA) gene (rDNA) transcription by RNA Polymerase I (Pol I) drives cell growth and underlies nucleolar structure and function, indirectly coordinating many fundamental cellular processes. The importance of keeping rDNA transcription under tight control is reflected by the fact that deranged Pol I transcription is a feature of cancer and other human disorders. In this review, we discuss multiple aspects of rDNA function including the relationship between Pol I transcription and proliferative capacity, the role of Pol I transcription in mediating nucleolar structure and integrity, and rDNA/nucleolar interactions with the genome and their influence on heterochromatin and global genome stability. Furthermore, we discuss how perturbations in the structure of the rDNA loci might contribute to human disease, in some cases independent of effects on ribosome biogenesis.

Keywords: Nucleoli; RNA Polymerase I; UBF; rDNA.

Publication types

Review