HNRPU explained

Heterogeneous nuclear ribonucleoprotein U is a protein that in humans is encoded by the HNRNPU gene.^{[1] [2]}

Function

This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins that form complexes with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene contains a RNA binding domain and scaffold-associated region (SAR)-specific bipartite DNA-binding domain. This protein is also thought to be involved in the packaging of hnRNA into large ribonucleoprotein complexes. During apoptosis, this protein is cleaved in a caspase-dependent way. Cleavage occurs at the SALD site, resulting in a loss of DNA-binding activity and a concomitant detachment of this protein from nuclear structural sites. But this cleavage does not affect the function of the encoded protein in RNA metabolism. At least two alternatively spliced transcript variants have been identified for this gene.^[3]

Interactions

HNRPU has been shown to interact with:

• EP300,^[4]
• GTF2F1,^[5]
• Glucocorticoid receptor,^[6] and
• NDN.^[7]

References

Further reading

• Kiledjian M, Dreyfuss G . Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box. . EMBO J. . 11 . 7 . 2655–64 . 1992 . 1628625 . 556741 . 10.1002/j.1460-2075.1992.tb05331.x.
• Barel M, Balbo M, Gauffre A, Frade R . Binding sites of the Epstein-Barr virus and C3d receptor (CR2, CD21) for its three intracellular ligands, the p53 anti-oncoprotein, the p68 calcium binding protein and the nuclear p120 ribonucleoprotein. . Mol. Immunol. . 32 . 6 . 389–97 . 1995 . 7753047 . 10.1016/0161-5890(95)00005-Y .
• Sidorenko SP, Law CL, Chandran KA, Clark EA . Human spleen tyrosine kinase p72Syk associates with the Src-family kinase p53/56Lyn and a 120-kDa phosphoprotein. . Proc. Natl. Acad. Sci. U.S.A. . 92 . 2 . 359–63 . 1995 . 7831290 . 42739 . 10.1073/pnas.92.2.359 . 1995PNAS...92..359S . free .
• Jordan P, Heid H, Kinzel V, Kübler D . Major cell surface-located protein substrates of an ecto-protein kinase are homologs of known nuclear proteins. . Biochemistry . 33 . 49 . 14696–706 . 1995 . 7993898 . 10.1021/bi00253a007 .
• Liu Q, Dreyfuss G . A novel nuclear structure containing the survival of motor neurons protein. . EMBO J. . 15 . 14 . 3555–65 . 1996 . 8670859 . 451956 . 10.1002/j.1460-2075.1996.tb00725.x.
• Fujioka Y, Matozaki T, Noguchi T, Iwamatsu A, Yamao T, Takahashi N, Tsuda M, Takada T, Kasuga M . A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion. . Mol. Cell. Biol. . 16 . 12 . 6887–99 . 1997 . 8943344 . 231692 . 10.1128/MCB.16.12.6887.
• Dennehy KM, Broszeit R, Garnett D, Durrheim GA, Spruyt LL, Beyers AD . Thymocyte activation induces the association of phosphatidylinositol 3-kinase and pp120 with CD5. . Eur. J. Immunol. . 27 . 3 . 679–86 . 1997 . 9079809 . 10.1002/eji.1830270316 . 41540340 .
• Malik KF, Jaffe H, Brady J, Young WS . The class III POU factor Brn-4 interacts with other class III POU factors and the heterogeneous nuclear ribonucleoprotein U. . Brain Res. Mol. Brain Res. . 45 . 1 . 99–107 . 1997 . 9105675 . 10.1016/S0169-328X(96)00238-0 .
• Eggert M, Michel J, Schneider S, Bornfleth H, Baniahmad A, Fackelmayer FO, Schmidt S, Renkawitz R . The glucocorticoid receptor is associated with the RNA-binding nuclear matrix protein hnRNP U. . J. Biol. Chem. . 272 . 45 . 28471–8 . 1997 . 9353307 . 10.1074/jbc.272.45.28471 . free .
• Göhring F, Schwab BL, Nicotera P, Leist M, Fackelmayer FO . The novel SAR-binding domain of scaffold attachment factor A (SAF-A) is a target in apoptotic nuclear breakdown. . EMBO J. . 16 . 24 . 7361–71 . 1998 . 9405365 . 1170336 . 10.1093/emboj/16.24.7361 .
• Hahm B, Cho OH, Kim JE, Kim YK, Kim JH, Oh YL, Jang SK . Polypyrimidine tract-binding protein interacts with HnRNP L. . FEBS Lett. . 425 . 3 . 401–6 . 1998 . 9563502 . 10.1016/S0014-5793(98)00269-5 . free . 1998FEBSL.425..401H .
• Matsui M, Breau WC, Iwasaki S, Hagiwara S, Tamai Y, Mori C, Bloom ML, Jerry MB, Eddy EM, Taketo MM . Retrovirus integration site Mintb encoding the mouse homolog of hnRNP U. . J. Biochem. . 125 . 6 . 1104–14 . 1999 . 10348913 . 10.1093/oxfordjournals.jbchem.a022392 .
• Kim MK, Nikodem VM . hnRNP U inhibits carboxy-terminal domain phosphorylation by TFIIH and represses RNA polymerase II elongation. . Mol. Cell. Biol. . 19 . 10 . 6833–44 . 2000 . 10490622 . 84680 . 10.1128/MCB.19.10.6833.
• Kipp M, Schwab BL, Przybylski M, Nicotera P, Fackelmayer FO . Apoptotic cleavage of scaffold attachment factor A (SAF-A) by caspase-3 occurs at a noncanonical cleavage site. . J. Biol. Chem. . 275 . 7 . 5031–6 . 2000 . 10671544 . 10.1074/jbc.275.7.5031 . free .
• Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG . Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. . Nat. Neurosci. . 3 . 7 . 661–9 . 2000 . 10862698 . 10.1038/76615 . 1842/742 . 14392630 . free .
• Taniura H, Yoshikawa K . Necdin interacts with the ribonucleoprotein hnRNP U in the nuclear matrix. . J. Cell. Biochem. . 84 . 3 . 545–55 . 2002 . 11813259 . 10.1002/jcb.10047 . 5988824 .
• Lee J, Bedford MT . PABP1 identified as an arginine methyltransferase substrate using high-density protein arrays. . EMBO Rep. . 3 . 3 . 268–73 . 2002 . 11850402 . 1084016 . 10.1093/embo-reports/kvf052 .
• Davis M, Hatzubai A, Andersen JS, Ben-Shushan E, Fisher GZ, Yaron A, Bauskin A, Mercurio F, Mann M, Ben-Neriah Y . Pseudosubstrate regulation of the SCF(beta-TrCP) ubiquitin ligase by hnRNP-U. . Genes Dev. . 16 . 4 . 439–51 . 2002 . 11850407 . 155337 . 10.1101/gad.218702 .

Notes and References

1. Fackelmayer FO, Richter A . hnRNP-U/SAF-A is encoded by two differentially polyadenylated mRNAs in human cells . Biochim Biophys Acta . 1217 . 2 . 232–4 . Mar 1994 . 7509195 . 10.1016/0167-4781(94)90044-2 .
2. Fackelmayer FO, Richter A . Purification of two isoforms of hnRNP-U and characterization of their nucleic acid binding activity . Biochemistry . 33 . 34 . 10416–22 . Sep 1994 . 8068679 . 10.1021/bi00200a024 .
3. Web site: Entrez Gene: HNRNPU heterogeneous nuclear ribonucleoprotein U (scaffold attachment factor A).
4. Martens JH, Verlaan M, Kalkhoven E, Dorsman JC, Zantema A . Scaffold/matrix attachment region elements interact with a p300-scaffold attachment factor A complex and are bound by acetylated nucleosomes . Mol. Cell. Biol. . 22 . 8 . 2598–606 . Apr 2002 . 11909954 . 133732 . 10.1128/mcb.22.8.2598-2606.2002.
5. Kim MK, Nikodem VM . hnRNP U inhibits carboxy-terminal domain phosphorylation by TFIIH and represses RNA polymerase II elongation . Mol. Cell. Biol. . 19 . 10 . 6833–44 . Oct 1999 . 10490622 . 84680 . 10.1128/MCB.19.10.6833.
6. Eggert M, Michel J, Schneider S, Bornfleth H, Baniahmad A, Fackelmayer FO, Schmidt S, Renkawitz R . The glucocorticoid receptor is associated with the RNA-binding nuclear matrix protein hnRNP U . J. Biol. Chem. . 272 . 45 . 28471–8 . Nov 1997 . 9353307 . 10.1074/jbc.272.45.28471. free .
7. Taniura H, Yoshikawa K . Necdin interacts with the ribonucleoprotein hnRNP U in the nuclear matrix . J. Cell. Biochem. . 84 . 3 . 545–55 . 11813259 . 10.1002/jcb.10047 . 2002. 5988824 .