Nucleolus organizer regions (NORs) are
chromosomal regions crucial for the formation of the
nucleolus. In humans, the NORs are located on the short arms of the
acrocentric chromosomes 13, 14, 15, 21 and 22, the genes
RNR1,
RNR2,
RNR3,
RNR4, and
RNR5 respectively.[1] These regions code for
5.8S,
18S, and
28Sribosomal RNA.[1] The NORs are "sandwiched" between the
repetitive,
heterochromaticDNA sequences of the
centromeres and
telomeres.[1] The exact sequence of these regions is not included in the human reference genome as of 2016[1] or the GRCh38.p10 released January 6, 2017.[2] On 28 February 2019, GRCh38.p13 was released, which added the NOR sequences for the short arms of chromosomes 13, 14, 15, 21, and 22.[3] However, it is known that NORs contain
tandem copies of
ribosomal DNA (rDNA) genes.[1] Some sequences of flanking sequences proximal and distal to NORs have been reported.[4] The NORs of a
loris have been reported to be highly variable.[5] There are also DNA sequences related to rDNA that are on other chromosomes and may be involved in nucleoli formation.[6]
Silver-stained nucleolus organizer region (arrow) at the tip of a chromosome of the Gecko Lepidodactylus lugubris
Barbara McClintock first described the "nucleolar-organizing body" in Zea mays in 1934.[7] In
karyotype analysis, a
silver stain can be used to identify the NOR.[8][9] NORs can also be seen in nucleoli using silver stain, and that is being used to investigate cancerous changes.[10][11][12] NORs can also be seen using
antibodies directed against the protein
UBF, which binds to NOR DNA.[1]
Molecular biology
In addition to UBF, NORs also bind to
ATRX protein,
treacle,
sirtuin-7 and other proteins.[1] UBF has been identified as a mitotic "bookmark" of expressed rDNA, which allows it to resume
transcription quickly after
mitosis.[1] The distal flanking junction (DJ) of the NORs has been shown to associate with the periphery of nucleoli.[4] rDNA
operons in Escherichia coli have been found to cluster near each other, similar to a eukaryotic nucleolus.[13]
^Baicharoen S, Hirai Y, Srikulnath K, Kongprom U, Hirai H (2016). "Hypervariability of Nucleolus Organizer Regions in Bengal Slow Lorises, Nycticebus bengalensis (Primates, Lorisidae)". Cytogenetic and Genome Research. 149 (4): 267–273.
doi:
10.1159/000449145.
PMID27648559.
^Kupriyanova NS, Netchvolodov KK, Sadova AA, Cherepanova MD, Ryskov AP (2015). "Non-canonical ribosomal DNA segments in the human genome, and nucleoli functioning". Gene. 572 (2): 237–42.
doi:
10.1016/j.gene.2015.07.019.
PMID26164756.
^McClintock B (1934). "The relation of a particular chromosomal element to the development of the nucleoli in Zea mays". Zeitschrift für Zellforschung und Mikroskopische Anatomie. 21 (2): 294–328.
doi:
10.1007/BF00374060.
^Bloom SE, Goodpasture C (October 1976). "An improved technique for selective silver staining of nucleolar organizer regions in human chromosomes". Human Genetics. 34 (2): 199–206.
doi:
10.1007/bf00278889.
PMID63440.