Nuclear hubs built on RNAs and clustered organization of the genome |
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| Institution: | 1. Dipartimento di Fisica, Università di Napoli Federico II, and INFN Napoli, Complesso Universitario di Monte Sant’Angelo, 80126 Naples, Italy;2. Berlin Institute of Health (BIH), MDC-Berlin, Germany;1. Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Hannoversche Strasse 28, 10115 Berlin, Germany;2. Institute for Biology, Humboldt University of Berlin, Berlin, Germany;1. Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA;2. Laboratory of Epigenetics and Chromosome Biology, Department of Biomedical Research, Institute for Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, 45110 Ioannina, Greece |
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| Abstract: | RNAs play diverse roles in formation and function of subnuclear compartments, most of which are associated with active genes. NEAT1 and NEAT2/MALAT1 exemplify long non-coding RNAs (lncRNAs) known to function in nuclear bodies; however, we suggest that RNA biogenesis itself may underpin much nuclear compartmentalization. Recent studies show that active genes cluster with nuclear speckles on a genome-wide scale, significantly advancing earlier cytological evidence that speckles (aka SC-35 domains) are hubs of concentrated pre-mRNA metabolism. We propose the ‘karyotype to hub’ hypothesis to explain this organization: clustering of genes in the human karyotype may have evolved to facilitate the formation of efficient nuclear hubs, driven in part by the propensity of ribonucleoproteins (RNPs) to form large-scale condensates. The special capacity of highly repetitive RNAs to impact architecture is highlighted by recent findings that human satellite II RNA sequesters factors into abnormal nuclear bodies in disease, potentially co-opting a normal developmental mechanism. |
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| Keywords: | Non-coding RNA Nuclear structure Genome organization Speckles Chromosome bands |
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