Nuclear bodies (also known as nuclear domains or nuclear dots) are

biomolecular condensate In biochemistry, biomolecular condensates are a class of membrane-less organelles and organelle subdomains, which carry out specialized functions within the cell. Unlike many organelles, biomolecular condensate composition is not controlled ...

s, membraneless structures found in the

cell nuclei The cell nucleus (; : nuclei) is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have no nuclei, and a few others including osteoc ...

eukaryotic The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

cells. Nuclear bodies include Cajal bodies, the

nucleolus The nucleolus (; : nucleoli ) is the largest structure in the cell nucleus, nucleus of eukaryote, eukaryotic cell (biology), cells. It is best known as the site of ribosome biogenesis. The nucleolus also participates in the formation of signa ...

, nuclear speckles (also called splicing speckles), histone locus bodies, and

promyelocytic leukemia protein Promyelocytic leukemia protein (PML) (also known as MYL, RNF71, PP8675 or TRIM19) is the protein product of the ''PML'' gene. PML protein is a tumor suppressor protein required for the assembly of a number of nuclear structures, called PML-nucle ...

(PML) nuclear bodies (also called PML oncogenic dots). Nuclear bodies also include ND10s. ND stands for nuclear domain, and 10 refers to the number of dots seen. Additionally, a nuclear body subtype is a clastosome suggested to be a site of protein degradation. While biomolecular condensate is a term often used interchangeably with nuclear bodies, the term "condensates" implies the thermodynamic properties of the body are known. Thus, nuclear body (and sometimes nuclear compartment) is a term that is more general and encompasses structures where either the biophysical property is not a condensate or is currently untested. Nuclear bodies were first seen as prominent interchromatin structures in the nuclei of malignant or hyperstimulated animal cells identified using anti-sp100 autoantibodies from

primary biliary cirrhosis Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to buil ...

and subsequently the promyelocytic leukemia (PML) factor, but appear also to be elevated in many autoimmune and cancerous diseases. Nuclear dots are metabolically stable and resistant to nuclease digestion and salt extraction.

Structure

Formation and examples of nuclear membraneless compartments

Simple nuclear bodies (types I and II) and the shells of complex nuclear bodies (types III, IVa and V) consist of a non-chromatinic fibrillar material which is most likely proteinaceous. That nuclear bodies co-isolated with the nuclear matrix, and were linked to the fibrogranular nuclear matrix component by projections from the surface of the nuclear bodies. The primary components of the nuclear dots are the proteins sp100 nuclear antigen, LYSP100(a homolog of sp100), ISG20, PML antigen, NDP55 and 53kDa protein associated with the nuclear matrix. Other proteins, such as PIC1/SUMO-1, which are associated with

nuclear pore complex The nuclear pore complex (NPC), is a large protein complex giving rise to the nuclear pore. A great number of nuclear pores are studded throughout the nuclear envelope that surrounds the eukaryote cell nucleus. The pores enable the nuclear tra ...

also associate with nuclear dots. The proteins can reorganize in the nucleus, by increasing number of dispersion in response to different stress (stimulation or heat shock, respectively).

Function

One of the nuclear body proteins appears to be involved in transcriptional active regions. Expression of PML antigen and sp100 is responsive to interferons. Sp100 seems to have transcriptional transactivating properties. PML protein was reported to suppress growth and transformation, and specifically inhibits the infection of vesicular stomatitis virus (VSV) (a rhabdovirus) and influenza A virus, but not other types of viruses. The SUMO-1

ubiquitin Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 19 ...

like protein is responsible for modifying PML protein such that it is targeted to dots. whereas overexpression of PML results in programmed cell death. One hypothesized function of the dots is as a 'nuclear dump' or 'storage depot'. The nuclear bodies may not all perform the same function. Sp140 associates with certain bodies and appears to be involved in transcriptional activation. ND10 nuclear bodies have been shown to play a major role in

chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...

regulation. Nuclear bodies have been suggested to be involved in multiple aspects of gene regulation. By concentrating substrates and enzymes in these defined territories (i.e., pre-ribosomal RNA and associated ribosome biogenesis protein within the nucleolus), it is hypothesized that this may help increase the efficiency of the enzymatic reactions associated with the particular nuclear body. For example, nuclear speckles, once thought to be storage depots of splicing factors, have been now shown to concentrate splicing-promoting factors (e.g., components of the major and minor spliceosome) and pre-mRNA substrate molecules to boost the kinetic efficiency of the splicing reaction. Thus future studies will show whether other nuclear bodies play functional roles in various aspects of gene regulation, such as transcription, RNA modifications, ribosome biogenesis, and other nuclear processes.

Pathology

These, or similar, bodies have been found increased in the presence of lymphoid cancers and SLE (lupus). They are also observed at higher frequencies in

subacute sclerosing panencephalitis Subacute sclerosing panencephalitis (SSPE), also known as Dawson disease, is a rare form of progressive brain inflammation caused by a persistent infection with the measles virus. The condition primarily affects children, teens, and young adults ...

; in this instance, antibodies to

measles Measles (probably from Middle Dutch or Middle High German ''masel(e)'', meaning "blemish, blood blister") is a highly contagious, Vaccine-preventable diseases, vaccine-preventable infectious disease caused by Measles morbillivirus, measles v ...

show expression in and localization to the nuclear bodies. * In promyelocytic leukemia (PML), the oncogenic PML- retinoic acid receptor alpha (RARalpha) chimera disrupts the normal concentration of PML in nuclear bodies. Administration of arsenic trioxide (As₂O₃) plus all-trans retinoic acid (Tretinoin) causes remission of this leukemia by triggering the bodies' reorganization. As₂O₃ destroys the chimera, allowing new SUMO-1 ubiquitinated PML to relocalize to nuclear bodies. Retinoic acid induces a caspase-3 mediated degradation of the same chimera. * In HHV, ICP0 disrupts nuclear dots in the early stage of infection.

References

{{Nucleus Autoimmune diseases D Autoantigens Cell nucleus