ILF3 explained

Interleukin enhancer-binding factor 3 is a protein that in humans is encoded by the ILF3 gene.^{[1] [2]}

Function

Nuclear factor of activated T-cells (NFAT) is a transcription factor required for T-cell expression of interleukin 2. NFAT binds to a sequence in the IL2 enhancer known as the antigen receptor response element 2. In addition, NFAT can bind RNA and is an essential component for encapsidation and protein priming of hepatitis B viral polymerase. NFAT is a heterodimer of 45 kDa and 90 kDa proteins, the larger of which is the product of this gene. The encoded protein, which is primarily localized to ribosomes, probably regulates transcription at the level of mRNA elongation. At least three transcript variants encoding three different isoforms have been found for this gene.^[3]

Interactions

ILF3 has been shown to interact with:

• DNA-PKcs,^[4]
• FUS,^[5]
• PRMT1^{[6] [7]}
• Protein kinase R,^{[5] [8] [9] [10]} and
• XPO5.^[11]
• C5orf36^[12]

Small NF90/ILF3-associated RNAs (snaR) (~120 nucleotides long) and are known to interact with ILF3 double-stranded RNA-binding motifs.^[13] snaR-A is abundant in human testis and has been shown to associate with ribosomes in HeLa cells. snaR-A is present in human and gorilla but not in chimpanzee. Other snaR RNAs are found in African Great Apes (including chimpanzee and bonobo).^[14]

ILF2 and ILF3 have been identified as autoantigens in mice with induced lupus,^{[15] [16]} in canine systemic rheumatic autoimmune disease,^[17] and as a rare finding in humans with autoimmune disease.^[18]

References

Further reading

• St Johnston D, Brown NH, Gall JG, Jantsch M . A conserved double-stranded RNA-binding domain . Proceedings of the National Academy of Sciences of the United States of America . 89 . 22 . 10979–83 . November 1992 . 1438302 . 50466 . 10.1073/pnas.89.22.10979 . 1992PNAS...8910979S . free .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–13 . April 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–8 . April 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Ting NS, Kao PN, Chan DW, Lintott LG, Lees-Miller SP . DNA-dependent protein kinase interacts with antigen receptor response element binding proteins NF90 and NF45 . The Journal of Biological Chemistry . 273 . 4 . 2136–45 . January 1998 . 9442054 . 10.1074/jbc.273.4.2136 . 10.1.1.615.1747 . 8781571 . free .
• Marcoulatos P, Avgerinos E, Tsantzalos DV, Vamvakopoulos NC . Mapping interleukin enhancer binding factor 3 gene (ILF3) to human chromosome 19 (19q11-qter and 19p11-p13.1) by polymerase chain reaction amplification of human-rodent somatic cell hybrid DNA templates . Journal of Interferon & Cytokine Research . 18 . 5 . 351–5 . May 1998 . 9620363 . 10.1089/jir.1998.18.351 .
• Aoki Y, Zhao G, Qiu D, Shi L, Kao PN . CsA-sensitive purine-box transcriptional regulator in bronchial epithelial cells contains NF45, NF90, and Ku . The American Journal of Physiology . 275 . 6 Pt 1 . L1164–72 . December 1998 . 9843854 . 10.1152/ajplung.1998.275.6.L1164. 4401714 .
• Langland JO, Kao PN, Jacobs BL . Nuclear factor-90 of activated T-cells: A double-stranded RNA-binding protein and substrate for the double-stranded RNA-dependent protein kinase, PKR . Biochemistry . 38 . 19 . 6361–8 . May 1999 . 10320367 . 10.1021/bi982410u .
• Patel RC, Vestal DJ, Xu Z, Bandyopadhyay S, Guo W, Erme SM, Williams BR, Sen GC . DRBP76, a double-stranded RNA-binding nuclear protein, is phosphorylated by the interferon-induced protein kinase, PKR . The Journal of Biological Chemistry . 274 . 29 . 20432–7 . July 1999 . 10400669 . 10.1074/jbc.274.29.20432 . free .
• Satoh M, Shaheen VM, Kao PN, Okano T, Shaw M, Yoshida H, Richards HB, Reeves WH . Autoantibodies define a family of proteins with conserved double-stranded RNA-binding domains as well as DNA binding activity . The Journal of Biological Chemistry . 274 . 49 . 34598–604 . December 1999 . 10574923 . 10.1074/jbc.274.49.34598 . free .
• Xu YH, Grabowski GA . Molecular cloning and characterization of a translational inhibitory protein that binds to coding sequences of human acid beta-glucosidase and other mRNAs . Molecular Genetics and Metabolism . 68 . 4 . 441–54 . December 1999 . 10607473 . 10.1006/mgme.1999.2934 .
• Coolidge CJ, Patton JG . A new double-stranded RNA-binding protein that interacts with PKR . Nucleic Acids Research . 28 . 6 . 1407–17 . March 2000 . 10684936 . 111047 . 10.1093/nar/28.6.1407 .
• Tang J, Kao PN, Herschman HR . Protein-arginine methyltransferase I, the predominant protein-arginine methyltransferase in cells, interacts with and is regulated by interleukin enhancer-binding factor 3 . The Journal of Biological Chemistry . 275 . 26 . 19866–76 . June 2000 . 10749851 . 10.1074/jbc.M000023200 . free .
• Saunders LR, Jurecic V, Barber GN . The 90- and 110-kDa human NFAR proteins are translated from two differentially spliced mRNAs encoded on chromosome 19p13 . Genomics . 71 . 2 . 256–9 . January 2001 . 11161820 . 10.1006/geno.2000.6423 .
• Duchange N, Pidoux J, Camus E, Sauvaget D . Alternative splicing in the human interleukin enhancer binding factor 3 (ILF3) gene . Gene . 261 . 2 . 345–53 . December 2000 . 11167023 . 10.1016/S0378-1119(00)00495-9 .
• Saunders LR, Perkins DJ, Balachandran S, Michaels R, Ford R, Mayeda A, Barber GN . Characterization of two evolutionarily conserved, alternatively spliced nuclear phosphoproteins, NFAR-1 and -2, that function in mRNA processing and interact with the double-stranded RNA-dependent protein kinase, PKR . The Journal of Biological Chemistry . 276 . 34 . 32300–12 . August 2001 . 11438536 . 10.1074/jbc.M104207200 . free .
• Parker LM, Fierro-Monti I, Mathews MB . Nuclear factor 90 is a substrate and regulator of the eukaryotic initiation factor 2 kinase double-stranded RNA-activated protein kinase . The Journal of Biological Chemistry . 276 . 35 . 32522–30 . August 2001 . 11438540 . 10.1074/jbc.M104408200 . free .
• Reichman TW, Muñiz LC, Mathews MB . The RNA binding protein nuclear factor 90 functions as both a positive and negative regulator of gene expression in mammalian cells . Molecular and Cellular Biology . 22 . 1 . 343–56 . January 2002 . 11739746 . 134226 . 10.1128/MCB.22.1.343-356.2002 .

Notes and References

1. Kao PN, Chen L, Brock G, Ng J, Kenny J, Smith AJ, Corthésy B . Cloning and expression of cyclosporin A- and FK506-sensitive nuclear factor of activated T-cells: NF45 and NF90 . The Journal of Biological Chemistry . 269 . 32 . 20691–9 . August 1994 . 10.1016/S0021-9258(17)32048-3 . 7519613 . free .
2. Matsumoto-Taniura N, Pirollet F, Monroe R, Gerace L, Westendorf JM . Identification of novel M phase phosphoproteins by expression cloning . Molecular Biology of the Cell . 7 . 9 . 1455–69 . September 1996 . 8885239 . 275994 . 10.1091/mbc.7.9.1455 .
3. Web site: Entrez Gene: ILF3 interleukin enhancer binding factor 3, 90kDa.
4. Ting NS, Kao PN, Chan DW, Lintott LG, Lees-Miller SP . DNA-dependent protein kinase interacts with antigen receptor response element binding proteins NF90 and NF45 . The Journal of Biological Chemistry . 273 . 4 . 2136–45 . January 1998 . 9442054 . 10.1074/jbc.273.4.2136 . 10.1.1.615.1747 . 8781571 . free .
5. Saunders LR, Perkins DJ, Balachandran S, Michaels R, Ford R, Mayeda A, Barber GN . Characterization of two evolutionarily conserved, alternatively spliced nuclear phosphoproteins, NFAR-1 and -2, that function in mRNA processing and interact with the double-stranded RNA-dependent protein kinase, PKR . The Journal of Biological Chemistry . 276 . 34 . 32300–12 . August 2001 . 11438536 . 10.1074/jbc.M104207200 . free .
6. Tang J, Kao PN, Herschman HR . Protein-arginine methyltransferase I, the predominant protein-arginine methyltransferase in cells, interacts with and is regulated by interleukin enhancer-binding factor 3 . The Journal of Biological Chemistry . 275 . 26 . 19866–76 . June 2000 . 10749851 . 10.1074/jbc.M000023200 . free .
7. Lee J, Bedford MT . PABP1 identified as an arginine methyltransferase substrate using high-density protein arrays . EMBO Reports . 3 . 3 . 268–73 . March 2002 . 11850402 . 1084016 . 10.1093/embo-reports/kvf052 .
8. Langland JO, Kao PN, Jacobs BL . Nuclear factor-90 of activated T-cells: A double-stranded RNA-binding protein and substrate for the double-stranded RNA-dependent protein kinase, PKR . Biochemistry . 38 . 19 . 6361–8 . May 1999 . 10320367 . 10.1021/bi982410u .
9. Parker LM, Fierro-Monti I, Mathews MB . Nuclear factor 90 is a substrate and regulator of the eukaryotic initiation factor 2 kinase double-stranded RNA-activated protein kinase . The Journal of Biological Chemistry . 276 . 35 . 32522–30 . August 2001 . 11438540 . 10.1074/jbc.M104408200 . free .
10. Patel RC, Vestal DJ, Xu Z, Bandyopadhyay S, Guo W, Erme SM, Williams BR, Sen GC . DRBP76, a double-stranded RNA-binding nuclear protein, is phosphorylated by the interferon-induced protein kinase, PKR . The Journal of Biological Chemistry . 274 . 29 . 20432–7 . July 1999 . 10400669 . 10.1074/jbc.274.29.20432 . free .
11. Brownawell AM, Macara IG . Exportin-5, a novel karyopherin, mediates nuclear export of double-stranded RNA binding proteins . The Journal of Cell Biology . 156 . 1 . 53–64 . January 2002 . 11777942 . 2173575 . 10.1083/jcb.200110082 .
12. Chu L, Su MY, Maggi LB, Lu L, Mullins C, Crosby S, Huang G, Chng WJ, Vij R, Tomasson MH . Multiple myeloma-associated chromosomal translocation activates orphan snoRNA ACA11 to suppress oxidative stress . The Journal of Clinical Investigation . 122 . 8 . 2793–806 . August 2012 . 22751105 . 3408744 . 10.1172/jci63051 .
13. Parrott AM, Mathews MB . Novel rapidly evolving hominid RNAs bind nuclear factor 90 and display tissue-restricted distribution . Nucleic Acids Research . 35 . 18 . 6249–58 . 2007 . 17855395 . 2094060 . 10.1093/nar/gkm668 .
14. Parrott AM, Tsai M, Batchu P, Ryan K, Ozer HL, Tian B, Mathews MB . The evolution and expression of the snaR family of small non-coding RNAs . Nucleic Acids Research . 39 . 4 . 1485–500 . March 2011 . 20935053 . 3045588 . 10.1093/nar/gkq856 .
15. Satoh M, Shaheen VM, Kao PN, Okano T, Shaw M, Yoshida H, Richards HB, Reeves WH . Autoantibodies define a family of proteins with conserved double-stranded RNA-binding domains as well as DNA binding activity . The Journal of Biological Chemistry . 274 . 49 . 34598–604 . December 1999 . 10574923 . 10.1074/jbc.274.49.34598 . free .
16. Kuroda Y, Ono N, Akaogi J, Nacionales DC, Yamasaki Y, Barker TT, Reeves WH, Satoh M . Induction of lupus-related specific autoantibodies by non-specific inflammation caused by an intraperitoneal injection of n-hexadecane in BALB/c mice . Toxicology . 218 . 2–3 . 186–96 . February 2006 . 16309812 . 10.1016/j.tox.2005.10.011 .
17. Bremer HD, Landegren N, Sjöberg R, Hallgren Å, Renneker S, Lattwein E, Leonard D, Eloranta ML, Rönnblom L, Nordmark G, Nilsson P, Andersson G, Lilliehöök I, Lindblad-Toh K, Kämpe O, Hansson-Hamlin H . ILF2 and ILF3 are autoantigens in canine systemic autoimmune disease . Scientific Reports . 8 . 1 . 4852 . March 2018 . 29556082 . 5859008 . 10.1038/s41598-018-23034-w . 2018NatSR...8.4852B .
18. Satoh M, Shaheen VM, Kao PN, Okano T, Shaw M, Yoshida H, Richards HB, Reeves WH . Autoantibodies define a family of proteins with conserved double-stranded RNA-binding domains as well as DNA binding activity . The Journal of Biological Chemistry . 274 . 49 . 34598–604 . December 1999 . 10574923 . 10.1074/jbc.274.49.34598 . free .