HNRNPC explained

Heterogeneous nuclear ribonucleoproteins C1/C2 is a protein that in humans is encoded by the HNRNPC gene.^{[1] [2]}

It is abnormally expressed in fetuses of both IVF and ICSI, which may contribute to the increase risk of birth defects in these ART.^[3]

Function

This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing(reference: Koenig J. nature structural and Molecular Biology 2010: iCLIP) 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. Transcriptional regulation by hormonal 1,25-dihydroxyvitamin D(3) (calcitriol) involves occupancy of vitamin D response elements (VDREs) by HNRNPC or 1,25(OH)(2)D(3)-bound vitamin D receptor (VDR).^{[4] [5] [6]} This relationship is disrupted by elevated HNRNPC, causing a form of hereditary vitamin D-resistant rickets (HVDRR) in both humans^[4] and non-human primates.^[7] The protein encoded by this gene can act as a tetramer and is involved in the assembly of 40S hnRNP particles. Species-specific tetramerization of HNRNPC subunits is important to its nucleic acid binding, whereby over-expression of major human HNRNPC subunits in mouse osteoblastic cells confers vitamin D resistance.^[8] Multiple transcript variants encoding at least two different isoforms have been described for this gene.^[2]

Interactions

HNRNPC has been shown to interact with Grb2.^[9]

Further reading

• Görlach M, Wittekind M, Beckman RA, Mueller L, Dreyfuss G . Interaction of the RNA-binding domain of the hnRNP C proteins with RNA . EMBO J. . 11 . 9 . 3289–95 . 1992 . 10.1002/j.1460-2075.1992.tb05407.x . 1380452 . 556863 .
• Wittekind M, Görlach M, Friedrichs M, Dreyfuss G, Mueller L . 1H, 13C, and 15N NMR assignments and global folding pattern of the RNA-binding domain of the human hnRNP C proteins . Biochemistry . 31 . 27 . 6254–65 . 1992 . 1385725 . 10.1021/bi00142a013 .
• Burd CG, Swanson MS, Görlach M, Dreyfuss G . Primary structures of the heterogeneous nuclear ribonucleoprotein A2, B1, and C2 proteins: a diversity of RNA binding proteins is generated by small peptide inserts . Proc. Natl. Acad. Sci. U.S.A. . 86 . 24 . 9788–92 . 1990 . 2557628 . 298587 . 10.1073/pnas.86.24.9788 . 1989PNAS...86.9788B . free .
• Merrill BM, Barnett SF, LeStourgeon WM, Williams KR . Primary structure differences between proteins C1 and C2 of HeLa 40S nuclear ribonucleoprotein particles . Nucleic Acids Res. . 17 . 21 . 8441–9 . 1989 . 2587210 . 335017 . 10.1093/nar/17.21.8441 .
• Swanson MS, Nakagawa TY, LeVan K, Dreyfuss G . Primary structure of human nuclear ribonucleoprotein particle C proteins: conservation of sequence and domain structures in heterogeneous nuclear RNA, mRNA, and pre-rRNA-binding proteins . Mol. Cell. Biol. . 7 . 5 . 1731–9 . 1987 . 10.1128/mcb.7.5.1731 . 3110598 . 365274 .
• Sébillon P, Beldjord C, Kaplan JC, Brody E, Marie J . A T to G mutation in the polypyrimidine tract of the second intron of the human beta-globin gene reduces in vitro splicing efficiency: evidence for an increased hnRNP C interaction . Nucleic Acids Res. . 23 . 17 . 3419–25 . 1995 . 7567451 . 307219 . 10.1093/nar/23.17.3419 .
• Kato S, Sekine S, Oh SW, Kim NS, Umezawa Y, Abe N, Yokoyama-Kobayashi M, Aoki T . Construction of a human full-length cDNA bank . Gene . 150 . 2 . 243–50 . 1995 . 7821789 . 10.1016/0378-1119(94)90433-2 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Huang M, Rech JE, Northington SJ, Flicker PF, Mayeda A, Krainer AR, LeStourgeon WM . The C-protein tetramer binds 230 to 240 nucleotides of pre-mRNA and nucleates the assembly of 40S heterogeneous nuclear ribonucleoprotein particles . Mol. Cell. Biol. . 14 . 1 . 518–33 . 1994 . 10.1128/mcb.14.1.518 . 8264621 . 358402 .
• Hamilton BJ, Nagy E, Malter JS, Arrick BA, Rigby WF . Association of heterogeneous nuclear ribonucleoprotein A1 and C proteins with reiterated AUUUA sequences . J. Biol. Chem. . 268 . 12 . 8881–7 . 1993 . 10.1016/S0021-9258(18)52955-0 . 8473331 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Romero F, Ramos-Morales F, Domínguez A, Rios RM, Schweighoffer F, Tocqué B, Pintor-Toro JA, Fischer S, Tortolero M . Grb2 and its apoptotic isoform Grb3-3 associate with heterogeneous nuclear ribonucleoprotein C, and these interactions are modulated by poly(U) RNA . J. Biol. Chem. . 273 . 13 . 7776–81 . 1998 . 9516488 . 10.1074/jbc.273.13.7776 . free .
• Neubauer G, King A, Rappsilber J, Calvio C, Watson M, Ajuh P, Sleeman J, Lamond A, Mann M . Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex . Nat. Genet. . 20 . 1 . 46–50 . 1998 . 9731529 . 10.1038/1700 . 585778 .
• Sella O, Gerlitz G, Le SY, Elroy-Stein O . Differentiation-Induced Internal Translation of c-sis mRNA: Analysis of the cis Elements and Their Differentiation-Linked Binding to the hnRNP C Protein . Mol. Cell. Biol. . 19 . 8 . 5429–40 . 1999 . 10409733 . 84385 . 10.1128/mcb.19.8.5429.
• Wang W, Furneaux H, Cheng H, Caldwell MC, Hutter D, Liu Y, Holbrook N, Gorospe M . HuR Regulates p21 mRNA Stabilization by UV Light . Mol. Cell. Biol. . 20 . 3 . 760–9 . 2000 . 10629032 . 85192 . 10.1128/MCB.20.3.760-769.2000 .
• Spångberg K, Wiklund L, Schwartz S . HuR, a protein implicated in oncogene and growth factor mRNA decay, binds to the 3' ends of hepatitis C virus RNA of both polarities . Virology . 274 . 2 . 378–90 . 2000 . 10964780 . 10.1006/viro.2000.0461 . free .
• Shahied L, Braswell EH, LeStourgeon WM, Krezel AM . An antiparallel four-helix bundle orients the high-affinity RNA binding sites in hnRNP C: a mechanism for RNA chaperonin activity . J. Mol. Biol. . 305 . 4 . 817–28 . 2001 . 11162094 . 10.1006/jmbi.2000.4331 .
• Andersen JS, Lyon CE, Fox AH, Leung AK, Lam YW, Steen H, Mann M, Lamond AI . Directed proteomic analysis of the human nucleolus . Curr. Biol. . 12 . 1 . 1–11 . 2002 . 11790298 . 10.1016/S0960-9822(01)00650-9 . free . 2002CBio...12....1A .
• Stone JR, Collins T . Rapid phosphorylation of heterogeneous nuclear ribonucleoprotein C1/C2 in response to physiologic levels of hydrogen peroxide in human endothelial cells . J. Biol. Chem. . 277 . 18 . 15621–8 . 2002 . 11877401 . 10.1074/jbc.M112153200 . free .

Notes and References

1. Nakagawa TY, Swanson MS, Wold BJ, Dreyfuss G . Molecular cloning of cDNA for the nuclear ribonucleoprotein particle C proteins: a conserved gene family . Proc Natl Acad Sci U S A . 83 . 7 . 2007–11 . May 1986 . 3457372 . 323219 . 10.1073/pnas.83.7.2007 . 1986PNAS...83.2007N . free .
2. Web site: Entrez Gene: HNRPC heterogeneous nuclear ribonucleoprotein C (C1/C2).
3. Zhang Y, Zhang YL, Feng C, Wu YT, Liu AX, Sheng JZ, Cai J, Huang HF . Comparative proteomic analysis of human placenta derived from assisted reproductive technology . Proteomics . 8 . 20 . 4344–56 . September 2008 . 18792929 . 10.1002/pmic.200800294 . 206362532 .
4. Lisse TS, Liu T, Irmler M, Beckers J, Chen H, Adams JS, Hewison M . Gene targeting by the vitamin D response element binding protein reveals a role for vitamin D in osteoblast mTOR signaling. . FASEB J . 25 . 3 . 937–47 . March 2011 . 21123297 . 10.1096/fj.10-172577 . free . 3042839 .
5. Chen H, Hewison M, Adams JS . Functional characterization of heterogeneous nuclear ribonuclear protein C1/C2 in vitamin D resistance: a novel response element-binding protein. . J Biol Chem . 281 . 51 . 39114–20 . December 2006 . 17071612 . 10.1074/jbc.m608006200 . free .
6. Lisse TS, Hewison M, Adams JS . Hormone response element binding proteins: novel regulators of vitamin D and estrogen signaling. . Steroids . 76 . 4 . 331–9 . March 2011 . 21236284 . 10.1016/j.steroids.2011.01.002 . 3042887.
7. Adams JS, Chen H, Chun RF, Nguyen L, Wu S, Ren SY, Barsony J, Gacad MA . Novel regulators of vitamin D action and metabolism: Lessons learned at the Los Angeles zoo. . J Cell Biochem . 88 . 2 . 308–14 . Feb 2003 . 12520531 . 10.1002/jcb.10333 . 25970432 .
8. Lisse TS, Vadivel K, Bajaj SP, Chun RF, Hewison M, Adams JS . The heterodimeric structure of heterogeneous nuclear ribonucleoprotein C1/C2 dictates 1,25-dihydroxyvitamin D-directed transcriptional events in osteoblasts. . Bone Research . 2 . July 2014 . 14011– . 25506471 . 4261231 . 10.1038/boneres.2014.11 .
9. Romero F, Ramos-Morales F, Domínguez A, Rios RM, Schweighoffer F, Tocqué B, Pintor-Toro JA, Fischer S, Tortolero M . Grb2 and its apoptotic isoform Grb3-3 associate with heterogeneous nuclear ribonucleoprotein C, and these interactions are modulated by poly(U) RNA . J. Biol. Chem. . 273 . 13 . 7776–81 . Mar 1998 . 9516488 . 10.1074/jbc.273.13.7776 . free .