Alternative titles; symbols
HGNC Approved Gene Symbol: PSPC1
Cytogenetic location: 13q12.11 Genomic coordinates (GRCh38): 13:19,671,205-19,782,945 (from NCBI)
By mass spectrometry of proteins isolated from purified HeLa cell nucleoli, Andersen et al. (2002) identified PSPC1, which they called PSP1. By SDS-PAGE, PSP1 had an apparent molecular mass of about 66.3 kD.
By EST database analysis and PCR, Fox et al. (2002) obtained 2 splice variants of PSPC1, which they called PSP1-alpha and -beta. The deduced 523-amino acid PSP1-alpha protein has a calculated molecular mass of 58.7 kD. PSP1-beta contains 393 amino acids and is identical to PSP1-alpha for the first 386 amino acids. Both PSP1 isoforms have 2 RNA-binding domains in their N-terminal halves. Northern blot analysis detected ubiquitous expression of at least 2 PSP1 transcripts of about 2.5 kb. Both PSP1 isoforms colocalized with p54NRB (NONO; 300084) and PSP2 (RBM14; 612409) in nucleoplasmic structures called paraspeckles, which were adjacent to but distinct from SC35 (SFRS2; 600813)-containing splicing speckles.
Fox et al. (2002) found that PSP1, PSP2, and p54NRB relocalized from paraspeckles to the perinucleolar cap region upon transcriptional blockade.
By histochemical analysis of HeLa cells using PSP1 as a marker protein, Fox et al. (2005) found that paraspeckles persisted throughout interphase and during most of mitosis, and only disappeared once daughter nuclei formed in telophase. The authors noted that this behavior contrasts with the behavior of other nuclear bodies, which disassemble when cells enter mitosis. In telophase, before transcription recommenced after cell division, fluorescence-tagged PSP1 transiently colocalized with newly formed nucleoli at perinucleolar caps. Immunoprecipitation and protein pull-down experiments showed that PSP1 formed a heterodimer with p54NRB. Mutation analysis showed that targeting of PSP1 to paraspeckles required either of its RNA-binding domains and its C-terminal coiled-coil domain, whereas accumulation of PSP1 at perinucleolar caps and its interaction with p54NRB required only the C-terminal coiled-coil domain. Since p54NRB predominantly forms a complex with PSF (SFPQ; 605199), Fox et al. (2005) suggested that a small proportion of p54NRP interacts with PSP1 and that this interaction, in addition to binding RNA, is required for targeting of PSP1 to paraspeckles and perinucleolar caps.
TET proteins, such as TET2 (612839), regulate DNA-methylation status by oxidizing 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), which can both serve as a stable epigenetic mark and participate in active demethylation. Using immunoprecipitation and coimmunoprecipitation experiments, Guallar et al. (2018) showed that Tet2, which lacks a DNA-binding domain, interacted with the RNA-binding protein Pspc1 in mouse embryonic stem cells (ESCs). Pspc1 recruited Tet2 to chromatin through RNA. Tet2 chromatin occupancy took place at transcriptionally active loci that transcribed RNAs bound to Pspc1. Identification of Pspc1 target RNAs revealed that Pspc1 bound to retrotransposable elements (REs), vestiges of ancient endogenous retrovirus (ERV) infection, and that this binding in turn regulated neighboring genes. The mechanisms for Pspc1/Tet2-mediated ERV regulation were distinct among different ERV classes. In particular, Pspc1 and Tet2 participated in repression of class III ERVs (i.e., MERVL) by mediating 5hmC modification of MERVL RNAs, leading to their degradation in ESCs. However, catalytic Tet2 activity and 5hmC-mediated RNA degradation were not the only mechanism for MERVL repression, as Pspc1 and Tet2 also appeared to act with Hdac1 (601241)/Hdac2 (605164) for transcriptional silencing of MERVL and regulation of its associated genes.
Hartz (2008) mapped the PSPC1 gene to chromosome 13q12.11 based on an alignment of the PSPC1 sequence (GenBank AF448795) with the genomic sequence (build 36.1).
Andersen, J. S., Lyon, C. E., Fox, A. H., Leung, A. K. L., Lam, Y. W., Steen, H., Mann, M., Lamond, A. I. Directed proteomic analysis of the human nucleolus. Curr. Biol. 12: 1-11, 2002. [PubMed: 11790298] [Full Text: https://doi.org/10.1016/s0960-9822(01)00650-9]
Fox, A. H., Bond, C. S., Lamond, A. I. P54nrb forms a heterodimer with PSP1 that localizes to paraspeckles in an RNA-dependent manner. Molec. Biol. Cell 16: 5304-5315, 2005. [PubMed: 16148043] [Full Text: https://doi.org/10.1091/mbc.e05-06-0587]
Fox, A. H., Lam, Y. W., Leung, A. K. L., Lyon, C. E., Andersen, J., Mann, M., Lamond, A. I. Paraspeckles: a novel nuclear domain. Curr. Biol. 12: 13-25, 2002. [PubMed: 11790299] [Full Text: https://doi.org/10.1016/s0960-9822(01)00632-7]
Guallar, D., Bi, X., Pardavila, J. A., Huang, X., Saenz, C., Shi, X., Zhou, H., Faiola, F., Ding, J., Haruehanroengra, P., Yang, F., Li, D., and 13 others. RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells. Nature Genet. 50: 443-451, 2018. [PubMed: 29483655] [Full Text: https://doi.org/10.1038/s41588-018-0060-9]
Hartz, P. A. Personal Communication. Baltimore, Md. 11/17/2008.