In anatomy

Anatomy

Anatomy is a branch of biology and medicine that is the consideration of the structure of living things. It is a general term that includes human anatomy, animal anatomy , and plant anatomy...

, a paraspeckle is an irregularly shaped sub-cellular

Cell (biology)

The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 compartment, approximately 0.2-1 μm in size, found in the nucleus

Cell nucleus

In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

' interchromatin

Chromatin

Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...

 space. First documented in HeLa

HeLa

A HeLa cell is a cell type in an immortal cell line used in scientific research. It is the oldest and most commonly used human cell line. The line was derived from cervical cancer cells taken on February 8, 1951 from Henrietta Lacks, a patient who eventually died of her cancer on October 4, 1951...

 cells, where there are generally 10-30 per nucleus, paraspeckles are now known to also exist in all human primary cells, transformed cell lines and tissue sections. Their name is derived from their distribution in the nucleus; the "para" is short for parallel and the "speckle" refers to the splicing speckles to which they are always in close proximity.

Localization

Paraspeckles are dynamic structures that are altered in response to changes in cellular metabolic activity. They are transcription dependent. All five of the proposed protein components have RNA

RNA

Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 recognition motifs (RRMs) and, in the absence of RNA polymerase II

RNA polymerase II

RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...

 transcription

Transcription (genetics)

Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

, the paraspeckle disappears and all of its associated proponents form a crescent shaped perinucleolar cap in the nucleolus. This phenomenon is demonstrated during the cell cycle. In the cell cycle, paraspeckles are present during interphase

Interphase

Interphase is the phase of the cell cycle in which the cell spends the majority of its time and performs the majority of its purposes including preparation for cell division. In preparation for cell division, it increases its size and makes a copy of its DNA...

 and during all of mitosis

Mitosis

Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

 except for telophase

Telophase

Telophase from the ancient Greek "τελος" and "φασις" , is a stage in both meiosis and mitosis in a eukaryotic cell. During telophase, the effects of prophase and prometaphase events are reversed. Two daughter nuclei form in the cell. The nuclear envelopes of the daughter cells are formed from the...

 because, when the two daughter nuclei are formed, there is no RNA Pol II transcription so the protein components instead form a perinucleolar cap. The localization patterns were also duplicated in experiments using transcription inhibiting drugs.

Function

The function of the paraspeckle nuclear domain, as a whole, is still not well understood. It has been postulated that the activity of p54nrb, a protein component, is dependent on its localization. It is therefore possible that the paraspeckle's role is to provide ordered localization of its component proteins and to thereby help direct their activity. It has also been suggested that the paraspeckle contributes to transcriptional regulation. Neither of these hypothesis, however, is universally accepted and therefore insight into the paraspeckle's larger role must be derived from the function of its protein components (PSP1, p54nrb, PSP2 and possibly CFI(m)68 and PSF).

The function of PSP1, the protein whose localization pattern led to the discovery of the paraspeckle, is not well understood. Myojin et al. speculated that PSP1, which is highly concentrated in the testis, may regulate the germ cell

Germ cell

A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate near the gut of an embryo and migrate to the developing gonads. There, they undergo cell division of two types, mitosis and meiosis, followed by...

s' early mRNA processing and assist in chromatin

Chromatin

Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...

 remodeling and nuclear shaping during spermatogenesis

Spermatogenesis

Spermatogenesis is the process by which male primary germ cells undergo division, and produce a number of cells termed spermatogonia, from which the primary spermatocytes are derived. Each primary spermatocyte divides into two secondary spermatocytes, and each secondary spermatocyte into two...

. PSP1 also forms a dimer with the second protein component: p54nrb. P54nrb has reported involvement in numerous nuclear events including "transcriptional regulation

Transcriptional regulation

Transcriptional regulation is the change in gene expression levels by altering transcription rates. -Regulation of transcription:Regulation of transcription controls when transcription occurs and how much RNA is created...

, splicing

Splicing (genetics)

In molecular biology and genetics, splicing is a modification of an RNA after transcription, in which introns are removed and exons are joined. This is needed for the typical eukaryotic messenger RNA before it can be used to produce a correct protein through translation...

, DNA unwinding, nuclear retention of hyperedited dsRNA, viral RNA processing, control and cell proliferation, and circadian rhythm

Circadian rhythm

A circadian rhythm, popularly referred to as body clock, is an endogenously driven , roughly 24-hour cycle in biochemical, physiological, or behavioural processes. Circadian rhythms have been widely observed in plants, animals, fungi and cyanobacteria...

 maintenance". The final confirmed component, PSP2, is involved in RNA splicing and coactivates hormone receptor

Hormone receptor

A hormone receptor is a receptor protein on the surface of a cell or in its interior that binds to a specific hormone. The hormone causes many changes to take place in the cell....

s.

Later studies have led to the identification of two additional proteins that are likely components of the paraspeckle. In 2004 Dettwiler et al. revealed CFI(m)68 as a possible component of the paraspeckle. CFI(m)68 has been implicated with the preliminary step in pre-mRNA 3' end splicing. Fox et al.'s 2005 article also contains evidence of a possible fifth protein component of the paraspeckle: PSF. PSF can bind both RNA and DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 and interacts with pre-mRNA splicing proteins that work in conjunction with proteins like CFI(m)68. It can dimerize with p54nrb. Furthermore, it colocalizes with PSP1 both in the paraspeckle and, if in the presence of transcription inhibiting drugs, in the same perinucleolar cap. If PSF is in fact part of the paraspeckle that would help further substantiate an assertion by Myojin, et al. that paraspeckle components may participate in pre-mRNA splicing.

In 2005 a new role for paraspeckles in a novel method for controlling gene expression was reported by Prasanth et al. In this study, a nuclear enriched non-coding RNA (termed CTNRNA) was identified that specifically localised to paraspeckles in the nuclei of several cell types. The group found that the RNA was retained in the nucleus at paraspeckles, and was associated with the paraspeckle proteins P54nrb and PSP1, likely through direct interactions between the proteins and motifs in the 3' untranslated (3' UTR) region of the RNA. The CTN non-coding RNA is a longer transcript produced from a gene that also encodes the membrane protein MCAT2, a cationic amino acid transporter. When cells became stressed, the nuclear non-coding RNA levels were reduced, coupled with an increase in cytoplasmic signal for the MCAT2 mRNA and protein. This led the authors to speculate that the paraspeckles were effectively a storage site for the spliced and processed CTN RNA, that were able to release the RNA in a functional protein-encoding form when the cell received a signal. This shorter form was then free to be transported to the cytoplasm and used as a template for protein production. This 'Rapid Release Nuclear Retention mechanism' is thought to save the cell 25 minutes in the production of the mCAT2 protein, as the RNA has already been transcribed, processed and spliced whilst it is being held in the paraspeckles.

Future research

Though much about the paraspeckle—including its function—remains unknown, the sub-organelle

Organelle

In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....

 provides a model of the dynamic nature and of the spatial organization of the nucleus. Better understanding this may lead to therapies for molecular diseases caused by mis-organization of nuclear protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

.

External links

• The Nuclear Compartments:Paraspeckle page on the Nuclear Protein Database, written by Dr. Archa Fox and Dr. Wendy Bickmore, provides a factsheet and links to information on paraspeckle components.