Paraspeckle

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Discovered by Fox et al. in 2002, paraspeckles are irregularly shaped compartments, approximately 0.2-1 μm in size,[1] that are in the nucleus' interchromatin space [2]. First documented in HeLa cells, where there are generally 10-30 per nucleus[3], paraspeckles are now known to also exist in all human primary cells, transformed cell lines and tissue sections[4]. Their name is derived from their distribution in the nucleus; the "para" is short for parallel and the "speckles" refers to the splicing speckles to which they are always in close proximity[3].

Contents

[edit] Localization

An overlay of a fluorescence micrograph (green) onto a DIC image of a HeLa cell expressing a Yellow fluorescent Protein fusion of Paraspeckle Protein 1 (PSP1)
An overlay of a fluorescence micrograph (green) onto a DIC image of a HeLa cell expressing a Yellow fluorescent Protein fusion of Paraspeckle Protein 1 (PSP1)

Paraspeckles are dynamic structures that are altered in response to changes in cellular metabolic activity. They are transcription dependent[2]. All five of the proposed protein components have RNA recognition motifs (RRMs) [3] and, in the absence of RNA Pol II transcription, 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 and during all of mitosis except for telophase 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. [4]

[edit] 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 [4]. 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 [5]. Neither of these hypothesis, however, is universally accepted and therefore insight into the paraspeckle's larger role must be derived from the function of the 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 [2], is not well understood. Myojin et al. speculated that PSP1, which is highly concentrated in the testis, may regulate the germ cells' early mRNA processing and assist in chromatin remodeling and nuclear shaping during spermatogenesis [6]. PSP1 also forms dimmers with the second protein component: p54nrb. P54nrb has reported involvement in numerous nuclear events including "transcriptional regulation, splicing, DNA unwinding, nuclear retention of hyperedited dsRNA, viral RNA processing, control and cell proliferation, and circadian rhythm maintenance"[4]. The final confirmed component, PSP2, is involved in RNA splicing and coactivates hormone receptors[3].


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 [4]. PSF can bind both RNA and DNA and interacts with pre-mRNA splicing proteins that work in conjunction with proteins like CFI(m)68 [6]. 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 [4]. If both PSF are in fact part of the paraspeckle they would help further substantiate an assertion by Myojin, et al. that paraspeckle components may participate in pre-mRNA splicing.

[edit] Future Research

Though much about the paraspeckle- including its function- remains unknown, the sub-organelle 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 proteins [2].

[edit] References

  1. ^ Fox, Archa. Interview with R. Sundby. Paraspeckle Size., E-mail Correspondence. 2007-03-07.
  2. ^ a b c d Fox, A. et al (2002). Paraspeckles: A Novel Nuclear Domain. Current Biology 12: 13–25. 
  3. ^ a b c d Fox, Archa; Wendy Bickmore (2004). Nuclear Compartments: Paraspeckles.
  4. ^ a b c d e f Fox, A. et al (2005). P54nrb Forms a Heterodimer with PSP1 That Localizes to Paraspeckles in an RNA-dependent Manner. Molecular Biology of the Cell 16: 5304-5315. 
  5. ^ Schuldt, A. (2002). Proteomics of the nucleolus. Nature Cell Biology 4: E35. 
  6. ^ a b Reiko, M. et al (2004). Expression and Functional Significance of Mouse Paraspeckle Protein 1 on spermatogenesis. Biology of Reproduction 17: 926-932. 

[edit] 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.
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