Translin Explained

Translin is a DNA-binding protein that in humans is encoded by the TSN gene.^{[1] [2] [3]} Together with translin-associated factor X, translin forms the component 3 of promoter of RISC (C3PO) complex which facilitates endonucleolytic cleavage of the passenger strand during microRNA loading into the RNA-induced silencing complex (RISC).^{[4] [5] [6]}

Function

This gene encodes a DNA-binding protein which specifically recognizes conserved target sequences at the breakpoint junction of chromosomal translocations. Translin polypeptides form a multimeric structure that is responsible for its DNA-binding activity. Recombination-associated motifs and translin-binding sites are present at recombination hotspots and may serve as indicators of breakpoints in genes which are fused by translocations. These binding activities may play a crucial role in chromosomal translocation in lymphoid neoplasms.^[3]

Interactions

Translin has been shown to interact with PPP1R15A.^[7]

Further reading

• Aoki K, Suzuki K, Sugano T, Tasaka T, Nakahara K, Kuge O, Omori A, Kasai M . A novel gene, Translin, encodes a recombination hotspot binding protein associated with chromosomal translocations . Nature Genetics . 10 . 2 . 167–74 . Jun 1995 . 7663511 . 10.1038/ng0695-167 . 9678546 .
• 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 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Aoki K, Nakahara K, Ikegawa C, Seto M, Takahashi T, Minowada J, Strominger JL, Maziarz RT, Kasai M . Nuclear proteins binding to a novel target sequence within the recombination hotspot regions of Bcl-2 and the immunoglobulin DH gene family . Oncogene . 9 . 4 . 1109–15 . Apr 1994 . 8134113 .
• Aoki K, Ishida R, Kasai M . Isolation and characterization of a cDNA encoding a Translin-like protein, TRAX . FEBS Letters . 401 . 2–3 . 109–12 . Jan 1997 . 9013868 . 10.1016/S0014-5793(96)01444-5 . 46704829 .
• Kasai M, Matsuzaki T, Katayanagi K, Omori A, Maziarz RT, Strominger JL, Aoki K, Suzuki K . The translin ring specifically recognizes DNA ends at recombination hot spots in the human genome . The Journal of Biological Chemistry . 272 . 17 . 11402–7 . Apr 1997 . 9111049 . 10.1074/jbc.272.17.11402 . 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 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Hasegawa T, Isobe K . Evidence for the interaction between Translin and GADD34 in mammalian cells . Biochimica et Biophysica Acta (BBA) - General Subjects . 1428 . 2–3 . 161–8 . Aug 1999 . 10434033 . 10.1016/s0304-4165(99)00060-4 .
• Badge RM, Yardley J, Jeffreys AJ, Armour JA . Crossover breakpoint mapping identifies a subtelomeric hotspot for male meiotic recombination . Human Molecular Genetics . 9 . 8 . 1239–44 . May 2000 . 10767349 . 10.1093/hmg/9.8.1239 . free .
• Hosaka T, Kanoe H, Nakayama T, Murakami H, Yamamoto H, Nakamata T, Tsuboyama T, Oka M, Kasai M, Sasaki MS, Nakamura T, Toguchida J . Translin binds to the sequences adjacent to the breakpoints of the TLS and CHOP genes in liposarcomas with translocation t(12;6) . Oncogene . 19 . 50 . 5821–5 . Nov 2000 . 11126370 . 10.1038/sj.onc.1203943 . free . 2433/150205 . free .
• Chennathukuzhi VM, Kurihara Y, Bray JD, Hecht NB . Trax (translin-associated factor X), a primarily cytoplasmic protein, inhibits the binding of TB-RBP (translin) to RNA . The Journal of Biological Chemistry . 276 . 16 . 13256–63 . Apr 2001 . 11278549 . 10.1074/jbc.M009707200 . free .
• Lee SP, Fuior E, Lewis MS, Han MK . Analytical ultracentrifugation studies of translin: analysis of protein-DNA interactions using a single-stranded fluorogenic oligonucleotide . Biochemistry . 40 . 46 . 14081–8 . Nov 2001 . 11705401 . 10.1021/bi010302t .
• Erdemir T, Bilican B, Oncel D, Goding CR, Yavuzer U . DNA damage-dependent interaction of the nuclear matrix protein C1D with Translin-associated factor X (TRAX) . Journal of Cell Science . 115 . Pt 1 . 207–16 . Jan 2002 . 10.1242/jcs.115.1.207 . 11801738 . 11693/24740 . free .
• Han MK, Lin P, Paek D, Harvey JJ, Fuior E, Knutson JR . Fluorescence studies of pyrene maleimide-labeled translin: excimer fluorescence indicates subunits associate in a tail-to-tail configuration to form octamer . Biochemistry . 41 . 10 . 3468–76 . Mar 2002 . 11876655 . 10.1021/bi015901e .
• Sengupta K, Rao BJ . Translin binding to DNA: recruitment through DNA ends and consequent conformational transitions . Biochemistry . 41 . 51 . 15315–26 . Dec 2002 . 12484770 . 10.1021/bi026378m .
• Li K, Wang L, Cheng J, Lu YY, Zhang LX, Mu JS, Hong Y, Liu Y, Duan HJ, Wang G, Li L, Chen JM . Interaction between hepatitis C virus core protein and translin protein--a possible molecular mechanism for hepatocellular carcinoma and lymphoma caused by hepatitis C virus . World Journal of Gastroenterology . 9 . 2 . 300–3 . Feb 2003 . 12532453 . 10.3748/wjg.v9.i2.300 . 4611333 . free .
• Yang S, Cho YS, Chennathukuzhi VM, Underkoffler LA, Loomes K, Hecht NB . Translin-associated factor X is post-transcriptionally regulated by its partner protein TB-RBP, and both are essential for normal cell proliferation . The Journal of Biological Chemistry . 279 . 13 . 12605–14 . Mar 2004 . 14711818 . 10.1074/jbc.M313133200 . free .

Notes and References

1. Kasai M, Aoki K, Matsuo Y, Minowada J, Maziarz RT, Strominger JL . Recombination hotspot associated factors specifically recognize novel target sequences at the site of interchromosomal rearrangements in T-ALL patients with t(8;14)(q24;q11) and t(1;14)(p32;q11) . . 6 . 7 . 1017–25 . Jul 1994 . 7947454 . 10.1093/intimm/6.7.1017 .
2. Aoki K, Inazawa J, Takahashi T, Nakahara K, Kasai M . Genomic structure and chromosomal localization of the gene encoding translin, a recombination hotspot binding protein . Genomics . 43 . 2 . 237–41 . Jul 1997 . 9244443 . 10.1006/geno.1997.4796 .
3. Web site: Entrez Gene: TSN translin.
4. Liu Y, Ye X, Jiang F, Liang C, Chen D, Peng J, Kinch LN, Grishin NV, Liu Q . C3PO, an endoribonuclease that promotes RNAi by facilitating RISC activation . Science . 325 . 5941 . 750–3 . Aug 2009 . 19661431 . 10.1126/science.1176325 . 2855623. 2009Sci...325..750L .
5. Ye X, Huang N, Liu Y, Paroo Z, Huerta C, Li P, Chen S, Liu Q, Zhang H . Structure of C3PO and mechanism of human RISC activation . Nature Structural & Molecular Biology . 18 . 6 . 650–7 . Jun 2011 . 21552258 . 10.1038/nsmb.2032 . 3109212.
6. Ha M, Kim VN . Regulation of microRNA biogenesis . Nature Reviews Molecular Cell Biology . 15 . 8 . 509–24 . Aug 2014 . 25027649 . 10.1038/nrm3838 . 205495632 .
7. Hasegawa T, Isobe K . Evidence for the interaction between Translin and GADD34 in mammalian cells . Biochimica et Biophysica Acta (BBA) - General Subjects . 1428 . 2–3 . 161–8 . Aug 1999 . 10434033 . 10.1016/s0304-4165(99)00060-4 .