Heterogeneous nuclear ribonucleoproteins C1/C2 is a protein that in humans is encoded by the HNRNPCgene.[5][6]
It is abnormally expressed in fetuses of both IVF and ICSI, which may contribute to the increase risk of birth defects in these ART.[7]
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).[8][9][10] This relationship is disrupted by elevated HNRNPC, causing a form of hereditary vitamin D-resistant rickets (HVDRR) in both humans[8] and non-human primates.[11] 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.[12] Multiple transcript variants encoding at least two different isoforms have been described for this gene.[6]
^Adams JS, Chen H, Chun RF, Nguyen L, Wu S, Ren SY, Barsony J, Gacad MA (February 2003). "Novel regulators of vitamin D action and metabolism: Lessons learned at the Los Angeles zoo". J Cell Biochem. 88 (2): 308–14. doi:10.1002/jcb.10333. PMID12520531.
^Lisse TS, Vadivel K, Bajaj SP, Chun RF, Hewison M, Adams JS (July 2014). "The heterodimeric structure of heterogeneous nuclear ribonucleoprotein C1/C2 dictates 1,25-dihydroxyvitamin D-directed transcriptional events in osteoblasts". Bone Research. 2: 14011. doi:10.1038/boneres.2014.11. PMID25506471.
^Romero F, Ramos-Morales F, Domínguez A, Rios RM, Schweighoffer F, Tocqué B, Pintor-Toro JA, Fischer S, Tortolero M (March 1998). "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. doi:10.1074/jbc.273.13.7776. PMID9516488.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Wittekind M, Görlach M, Friedrichs M, Dreyfuss G, Mueller L (1992). "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. doi:10.1021/bi00142a013. PMID1385725.
Kato S, Sekine S, Oh SW, Kim NS, Umezawa Y, Abe N, Yokoyama-Kobayashi M, Aoki T (1995). "Construction of a human full-length cDNA bank". Gene. 150 (2): 243–50. doi:10.1016/0378-1119(94)90433-2. PMID7821789.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Hamilton BJ, Nagy E, Malter JS, Arrick BA, Rigby WF (1993). "Association of heterogeneous nuclear ribonucleoprotein A1 and C proteins with reiterated AUUUA sequences". J. Biol. Chem. 268 (12): 8881–7. PMID8473331.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Romero F, Ramos-Morales F, Domínguez A, Rios RM, Schweighoffer F, Tocqué B, Pintor-Toro JA, Fischer S, Tortolero M (1998). "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. doi:10.1074/jbc.273.13.7776. PMID9516488.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Neubauer G, King A, Rappsilber J, Calvio C, Watson M, Ajuh P, Sleeman J, Lamond A, Mann M (1998). "Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex". Nat. Genet. 20 (1): 46–50. doi:10.1038/1700. PMID9731529.
Spångberg K, Wiklund L, Schwartz S (2000). "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. doi:10.1006/viro.2000.0461. PMID10964780.
Shahied L, Braswell EH, LeStourgeon WM, Krezel AM (2001). "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. doi:10.1006/jmbi.2000.4331. PMID11162094.
Andersen JS, Lyon CE, Fox AH, Leung AK, Lam YW, Steen H, Mann M, Lamond AI (2002). "Directed proteomic analysis of the human nucleolus". Curr. Biol. 12 (1): 1–11. doi:10.1016/S0960-9822(01)00650-9. PMID11790298.
Stone JR, Collins T (2002). "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. doi:10.1074/jbc.M112153200. PMID11877401.{{cite journal}}: CS1 maint: unflagged free DOI (link)