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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Gene Review

BCYRN1  -  brain cytoplasmic RNA 1

Homo sapiens

Synonyms: BC200, BC200a, LINC00004, NCRNA00004
 
 
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Disease relevance of BCYRN1

  • BC200 RNA was expressed in carcinomas of the breast, cervix, oesophagus, lung, ovary, parotid, and tongue, but not in corresponding normal tissues [1].
  • BC200 RNA in invasive and preinvasive breast cancer [2].
  • In ductal carcinomas in situ, furthermore, significant BC200 expression was associated with high nuclear grade, suggesting that the presence of BC200 RNA in such tumors may be used as a prognostic indicator of tumor progression [2].
  • In this investigation, we have measured the abundance of the BC200 RNA transcript in total RNA isolated from 18 temporal neocortices (Brodman area 22) of brains with no pathology and those affected with neurodegenerative disease [3].
 

Psychiatry related information on BCYRN1

 

High impact information on BCYRN1

  • Interestingly, the BC200 beta pseudogene may have been generated by a conversion-like event after the human/chimpanzee divergence, resulting in an exchange of the left arm of a dimeric Alu element with the BC200 RNA coding sequence [5].
  • BC200 RNA: a neural RNA polymerase III product encoded by a monomeric Alu element [5].
  • The BC200 RNA gene is an early monomeric member and one of the few postulated transcriptionally active Alu sequences in this family of nearly half a million retropositionally amplified elements dispersed throughout the human genome [5].
  • The 3' sequence is unique to BC200 RNA and shows no apparent similarity with known human DNA sequences [6].
  • Moreover, like rat BC1 RNA, human BC200 RNA was localized to dendrite-rich neuropil areas, for example, in the inner plexiform layer of the retina [6].
 

Biological context of BCYRN1

  • Assignment of the human BC200 RNA gene (BCYRN1) to chromosome 2p16 by radiation hybrid mapping [7].
  • Furthermore, the isolation of two pseudogenes, BC200 beta and BC200 gamma, demonstrates the gene's transpositional ability [5].
  • The sequence upstream of the transcribed region in human annexin I contained a rare, Alu-like repetitive element with flanking direct repeats, probably derived from the active BC200 gene via germline retroposition [8].
  • The period following the divergence of New World monkeys and Old World monkeys from their common ancestor is characterized by a significantly higher substitution rate in the examined 5' flanking region than in the BC200 RNA coding region itself [9].
  • Therefore, our data also indicate that the neuronal BC200 RNP is a candidate for regulating decentralized protein biosynthesis in dendrites, possibly with a mechanism that resembles translation arrest of the SRP [10].
 

Anatomical context of BCYRN1

  • These results indicate that BC1 RNA and BC200 RNA, although of different evolutionary pedigree, may play analogous functional roles, in rodents and primates, respectively, in somatodendritic domains of nerve cells [6].
  • These findings lend support to the hypothesis that the BC1 and BC200 RNPs are involved in protein translation in neuronal dendrites [11].
  • Neuronal dendritic BC1 RNA and BC200 RNA and similar small untranslated RNAs inhibit protein translation in vitro systems, such as rabbit reticulocyte lysate [12].
  • BC200 RNA is not normally expressed in non-neuronal somatic cells; it has been shown, however, to be expressed in germ cells and in cultured immortal cell lines of various non-neural origins [1].
  • Nevertheless, in the micro-environment of dendritic spines of neuronal cells, BC1 RNPs or BC200 RNPs might mediate regulatory functions by differential interactions with locally limited PABP and/or directly or indirectly, with other translation initiation factors [12].
 

Associations of BCYRN1 with chemical compounds

  • Competition experiments using variants of BC1 and BC200 RNAs demonstrated that the central adenosine-rich region of both RNAs mediates binding to PABP [11].
  • In sucrose gradients, the BC200 particle has a sedimentation constant of about 11.4 S, significantly more than the corresponding 200 nucleotide long naked RNA (approximately 7.6 S) [13].
 

Physical interactions of BCYRN1

  • Here, we showed that the N terminus of FMRP binds strongly and specifically to BC1 and to its potential human analog BC200 [4].
  • Puralpha binds to human BC200 RNA, implicated in dendritic targeting, and this has homologies to 7SL RNA, implicated in compartmentalized translation [14].
  • Transgenic BC200 RNA is transported into neuronal dendrites as it is in human brain [15].
 

Other interactions of BCYRN1

  • Heterodimer SRP9/14 is an integral part of the neural BC200 RNP in primate brain [10].
  • Retronuons derived from small non-messenger RNAs (snmRNAs) generate novel snmRNA genes (such as the neuron-specific BC1 and BC200 RNAs) (Brosius, 1999b, Gene, 238, 115-134; Brosius and Gould, 1992, PROC: Natl Acad. Sci. USA, 89, 10706-10710) [16].
  • Poly(A)-binding protein is associated with neuronal BC1 and BC200 ribonucleoprotein particles [11].
  • Identification of human autoantigen La/SS-B as BC1/BC200 RNA-binding protein [17].
  • The BC200 gene, with sufficient upstream flanking sequences, is expressed in transgenic mouse brain areas comparable to those in human brain, and G22 gene, with upstream flanks, has a similar expression pattern [15].
 

Analytical, diagnostic and therapeutic context of BCYRN1

  • We have determined the primary structure of human BC200 RNA, using cDNA cloning and PCR techniques [6].
  • In situ hybridization to selected areas of the human nervous system showed that BC200 RNA is expressed by a subpopulation of neurons that is analogous to the BC1 RNA-expressing subset of neurons in the corresponding areas of the rat nervous system [6].

References

  1. Expression of neural BC200 RNA in human tumours. Chen, W., Böcker, W., Brosius, J., Tiedge, H. J. Pathol. (1997) [Pubmed]
  2. BC200 RNA in invasive and preinvasive breast cancer. Iacoangeli, A., Lin, Y., Morley, E.J., Muslimov, I.A., Bianchi, R., Reilly, J., Weedon, J., Diallo, R., Böcker, W., Tiedge, H. Carcinogenesis (2004) [Pubmed]
  3. BC200 RNA in normal human neocortex, non-Alzheimer dementia (NAD), and senile dementia of the Alzheimer type (AD). Lukiw, W.J., Handley, P., Wong, L., Crapper McLachlan, D.R. Neurochem. Res. (1992) [Pubmed]
  4. Fragile X mental retardation protein (FMRP) binds specifically to the brain cytoplasmic RNAs BC1/BC200 via a novel RNA-binding motif. Zalfa, F., Adinolfi, S., Napoli, I., Kühn-Hölsken, E., Urlaub, H., Achsel, T., Pastore, A., Bagni, C. J. Biol. Chem. (2005) [Pubmed]
  5. BC200 RNA: a neural RNA polymerase III product encoded by a monomeric Alu element. Martignetti, J.A., Brosius, J. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  6. Primary structure, neural-specific expression, and dendritic location of human BC200 RNA. Tiedge, H., Chen, W., Brosius, J. J. Neurosci. (1993) [Pubmed]
  7. Assignment of the human BC200 RNA gene (BCYRN1) to chromosome 2p16 by radiation hybrid mapping. Basile, V., Vicente, A., Martignetti, J.A., Skryabin, B.V., Brosius, J., Kennedy, J.L. Cytogenet. Cell Genet. (1998) [Pubmed]
  8. A BC200-derived element and Z-DNA as structural markers in annexin I genes: relevance to Alu evolution and annexin tetrad formation. Morgan, R.O., Fernández, M.P. J. Mol. Evol. (1995) [Pubmed]
  9. The BC200 RNA gene and its neural expression are conserved in Anthropoidea (Primates). Skryabin, B.V., Kremerskothen, J., Vassilacopoulou, D., Disotell, T.R., Kapitonov, V.V., Jurka, J., Brosius, J. J. Mol. Evol. (1998) [Pubmed]
  10. Heterodimer SRP9/14 is an integral part of the neural BC200 RNP in primate brain. Kremerskothen, J., Zopf, D., Walter, P., Cheng, J.G., Nettermann, M., Niewerth, U., Maraia, R.J., Brosius, J. Neurosci. Lett. (1998) [Pubmed]
  11. Poly(A)-binding protein is associated with neuronal BC1 and BC200 ribonucleoprotein particles. Muddashetty, R., Khanam, T., Kondrashov, A., Bundman, M., Iacoangeli, A., Kremerskothen, J., Duning, K., Barnekow, A., Hüttenhofer, A., Tiedge, H., Brosius, J. J. Mol. Biol. (2002) [Pubmed]
  12. Inhibitory effect of naked neural BC1 RNA or BC200 RNA on eukaryotic in vitro translation systems is reversed by poly(A)-binding protein (PABP). Kondrashov, A.V., Kiefmann, M., Ebnet, K., Khanam, T., Muddashetty, R.S., Brosius, J. J. Mol. Biol. (2005) [Pubmed]
  13. Expression of dendritic BC200 RNA, component of a 11.4S ribonucleoprotein particle, is conserved in humans and simians. Cheng, J.G., Tiedge, H., Brosius, J. Neurosci. Lett. (1997) [Pubmed]
  14. Role of Puralpha in targeting mRNA to sites of translation in hippocampal neuronal dendrites. Johnson, E.M., Kinoshita, Y., Weinreb, D.B., Wortman, M.J., Simon, R., Khalili, K., Winckler, B., Gordon, J. J. Neurosci. Res. (2006) [Pubmed]
  15. Two primate-specific small non-protein-coding RNAs in transgenic mice: neuronal expression, subcellular localization and binding partners. Khanam, T., Rozhdestvensky, T.S., Bundman, M., Galiveti, C.R., Handel, S., Sukonina, V., Jordan, U., Brosius, J., Skryabin, B.V. Nucleic Acids Res. (2007) [Pubmed]
  16. How significant is 98.5% 'junk' in mammalian genomes? Brosius, J. Bioinformatics (2003) [Pubmed]
  17. Identification of human autoantigen La/SS-B as BC1/BC200 RNA-binding protein. Kremerskothen, J., Nettermann, M., op de Bekke, A., Bachmann, M., Brosius, J. DNA Cell Biol. (1998) [Pubmed]
 
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