Actively transcribed rDNA and distal junction (DJ) sequence are involved in association of NORs with nucleoli.

Autor: Liskovykh M; Developmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD, 20892, USA. mikhail.liskovykh@nih.gov., Petrov NS; Developmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD, 20892, USA., Noskov VN; Developmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD, 20892, USA., Masumoto H; Laboratory of Chromosome Engineering, Department of Frontier Research and Development, Kazusa DNA Research Institute, Kisarazu, Chiba, 292-0818, Japan., Earnshaw WC; Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, EH9 3JR, Scotland, UK., Schlessinger D; National Institute on Aging, Laboratory of Genetics and Genomics, NIH, Baltimore, MD, 21224, USA., Shabalina SA; National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD, 20892, USA., Larionov V; Developmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD, 20892, USA. larionov@mail.nih.gov., Kouprina N; Developmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD, 20892, USA. kouprinn@mail.nih.gov.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2023 Apr 12; Vol. 80 (5), pp. 121. Date of Electronic Publication: 2023 Apr 12.
DOI: 10.1007/s00018-023-04770-3
Abstrakt: Although they are organelles without a limiting membrane, nucleoli have an exclusive structure, built upon the rDNA-rich acrocentric short arms of five human chromosomes (nucleolar organizer regions or NORs). This has raised the question: what are the structural features of a chromosome required for its inclusion in a nucleolus? Previous work has suggested that sequences adjacent to the tandemly repeated rDNA repeat units (DJ, distal junction sequence) may be involved, and we have extended such studies by addressing several issues related to the requirements for the association of NORs with nucleoli. We exploited both a set of somatic cell hybrids containing individual human acrocentric chromosomes and a set of Human Artificial Chromosomes (HACs) carrying different parts of a NOR, including an rDNA unit or DJ or PJ (proximal junction) sequence. Association of NORs with nucleoli was increased when constituent rDNA was transcribed and may be also affected by the status of heterochromatin blocks formed next to the rDNA arrays. Furthermore, our data suggest that a relatively small size DJ region, highly conserved in evolution, is also involved, along with the rDNA repeats, in the localization of p-arms of acrocentric chromosomes in nucleoli. Thus, we infer a cooperative action of rDNA sequence-stimulated by its activity-and sequences distal to rDNA contributing to incorporation into nucleoli. Analysis of NOR sequences also identified LncRNA_038958 in the DJ, a candidate transcript with the region of the suggested promoter that is located close to the DJ/rDNA boundary and contains CTCF binding sites. This LncRNA may affect RNA Polymerase I and/or nucleolar activity. Our findings provide the basis for future studies to determine which RNAs and proteins interact critically with NOR sequences to organize the higher-order structure of nucleoli and their function in normal cells and pathological states.
(© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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