Synthesis of the ribosomal RNA precursor in human cells: mechanisms, factors and regulation
Author:
Daiß Julia L.1ORCID, Griesenbeck Joachim1ORCID, Tschochner Herbert1ORCID, Engel Christoph1ORCID
Affiliation:
1. Regensburg Center for Biochemistry , University of Regensburg , D-93053 Regensburg , Germany
Abstract
Abstract
The ribosomal RNA precursor (pre-rRNA) comprises three of the four ribosomal RNAs and is synthesized by RNA polymerase (Pol) I. Here, we describe the mechanisms of Pol I transcription in human cells with a focus on recent insights gained from structure-function analyses. The comparison of Pol I-specific structural and functional features with those of other Pols and with the excessively studied yeast system distinguishes organism-specific from general traits. We explain the organization of the genomic rDNA loci in human cells, describe the Pol I transcription cycle regarding structural changes in the enzyme and the roles of human Pol I subunits, and depict human rDNA transcription factors and their function on a mechanistic level. We disentangle information gained by direct investigation from what had apparently been deduced from studies of the yeast enzymes. Finally, we provide information about how Pol I mutations may contribute to developmental diseases, and why Pol I is a target for new cancer treatment strategies, since increased rRNA synthesis was correlated with rapidly expanding cell populations.
Funder
Deutsche Forschungsgemeinschaft
Publisher
Walter de Gruyter GmbH
Subject
Clinical Biochemistry,Molecular Biology,Biochemistry
Reference189 articles.
1. Akamatsu, Y. and Kobayashi, T. (2015). The human RNA polymerase I transcription terminator complex acts as a replication fork barrier that coordinates the progress of replication with rRNA transcription activity. Mol. Cell Biol. 35: 1871–1881. 2. Albert, B., Colleran, C., Léger-Silvestre, I., Berger, A.B., Dez, C., Normand, C., Perez-Fernandez, J., McStay, B., and Gadal, O. (2013). Structure-function analysis of Hmo1 unveils an ancestral organization of HMG-Box factors involved in ribosomal DNA transcription from yeast to human. Nucleic Acids Res. 41: 10135–10149. 3. Albert, B., Léger-Silvestre, I., Normand, C., Ostermaier, M.K., Pérez-Fernández, J., Panov, K.I., Zomerdijk, J.C., Schultz, P., and Gadal, O. (2011). RNA polymerase I-specific subunits promote polymerase clustering to enhance the rRNA gene transcription cycle. J. Cell Biol. 192: 277–293. 4. Amann, S.J., Keihsler, D., Bodrug, T., Brown, N.G., and Haselbach, D. (2023) Frozen in time: analyzing molecular dynamics with time-resolved cryo-EM. Structure 31: 4–19. 5. Andrews, W.J., Ray, S., Panova, T., Engel, C., and Panov, K.I. (2021). DNA intercalators inhibit eukaryotic ribosomal RNA synthesis by impairing the initiation of transcription. Genes 12.
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