3sde

Structural highlights

Disease

[NONO_HUMAN] Translocation renal cell carcinoma. A chromosomal aberration involving NONO may be a cause of papillary renal cell carcinoma (PRCC). Translocation t(X;X)(p11.2;q13.1) with TFE3.

Function

[PSPC1_HUMAN] Regulates, cooperatively with NONO and SFPQ, androgen receptor-mediated gene transcription activity in Sertoli cell line (By similarity). Binds to poly(A), poly(G) and poly(U) RNA homopolymers (By similarity). Together with NONO, required for the formation of nuclear paraspeckles.^[1] [NONO_HUMAN] DNA- and RNA binding protein, involved in several nuclear processes. Binds the conventional octamer sequence in double-stranded DNA. Also binds single-stranded DNA and RNA at a site independent of the duplex site. Involved in pre-mRNA splicing, probably as a heterodimer with SFPQ. Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b. Together with PSPC1, required for the formation of nuclear paraspeckles. The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs. The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1. The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends. In vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex. NONO is involved in transcriptional regulation. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional avtivity. NONO binds to an enhancer element in long terminal repeats of endogenous intracisternal A particles (IAPs) and activates transcription. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer.^{[2] [3] [4] [5] [6]}

References

1. ↑ Passon DM, Lee M, Rackham O, Stanley WA, Sadowska A, Filipovska A, Fox AH, Bond CS. Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation. Proc Natl Acad Sci U S A. 2012 Mar 13. PMID:22416126 doi:10.1073/pnas.1120792109
2. ↑ Straub T, Knudsen BR, Boege F. PSF/p54(nrb) stimulates "jumping" of DNA topoisomerase I between separate DNA helices. Biochemistry. 2000 Jun 27;39(25):7552-8. PMID:10858305
3. ↑ Zhang Z, Carmichael GG. The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs. Cell. 2001 Aug 24;106(4):465-75. PMID:11525732
4. ↑ Sewer MB, Nguyen VQ, Huang CJ, Tucker PW, Kagawa N, Waterman MR. Transcriptional activation of human CYP17 in H295R adrenocortical cells depends on complex formation among p54(nrb)/NonO, protein-associated splicing factor, and SF-1, a complex that also participates in repression of transcription. Endocrinology. 2002 Apr;143(4):1280-90. PMID:11897684 doi:http://dx.doi.org/10.1210/endo.143.4.8748
5. ↑ Bladen CL, Udayakumar D, Takeda Y, Dynan WS. Identification of the polypyrimidine tract binding protein-associated splicing factor.p54(nrb) complex as a candidate DNA double-strand break rejoining factor. J Biol Chem. 2005 Feb 18;280(7):5205-10. Epub 2004 Dec 7. PMID:15590677 doi:http://dx.doi.org/10.1074/jbc.M412758200
6. ↑ Passon DM, Lee M, Rackham O, Stanley WA, Sadowska A, Filipovska A, Fox AH, Bond CS. Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation. Proc Natl Acad Sci U S A. 2012 Mar 13. PMID:22416126 doi:10.1073/pnas.1120792109
7. ↑ Passon DM, Lee M, Rackham O, Stanley WA, Sadowska A, Filipovska A, Fox AH, Bond CS. Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation. Proc Natl Acad Sci U S A. 2012 Mar 13. PMID:22416126 doi:10.1073/pnas.1120792109