Research

Research

2) Molecular mechanisms of telomere targeting and its application

Telomere is synthesized usually by telomerase, but some insects have no or very weak telomerase activity. We found that telomeric repeat-specific LINEs backup the telomere shortening in the silkworm and that it encodes the telomeric repeat cutting enzyme. We are trying to understand maintenance and evolution of insect telomeres through the investigation of telomere specific LINEs. The anti-telomerase reagent and telomere length regulation is thought to be a potent repressor for aging and tumorigenesis. Thus, we are also analyzing cutting mechanism of the telomere cutting enzyme in LINE, and attempting to apply it to the anti-tumor reagent.

Important papers are marked by yellow.

1) Fujiwara, H., Ogura, T., Takada, N., Miyajima, N., Ishikawa, H. and Maekawa, H.: Introns and their flanking sequences of Bombyx mori rDNA. Nucleic Acids Res. (1984) 12, 6861-6869.

2) Fujiwara, H., Ninaki, O., Kobayashi, M., Kusuda, J. and Maekawa, H.: Chromosomal fragment responsible for genetic mosaicism in larval body marking of the silkworm, Bombyx mori. Genet. Res. (1991) 57, 11-16.

3) Okazaki, S., Tsuchida, K., Maekawa, H., Ishikawa, H. and Fujiwara, H.: Identification of a pentanucleotide telomeric sequence, (TTAGG)n, in the silkworm, Bombyx mori and in other insects. Mol. Cell. Biol. (1993) 13, 1424-1432.

4) Fujiwara, H., Yanagawa, M. and Ishikawa, H.: Mosaic formation by developmental loss of chromosomal fragment in a genetic mosaic, mottled striped of the silkworm, Bombyx mori. Roux's Arch. Dev. Biol. (1994) 203, 389-396.

5) Fujiwara, H. and Maekawa, H.: RFLP analysis of chromosomal fragments in mottled striped strains of the silkworm, Bombyx mori. Chromosoma (1994) 103, 468-474.

6) Okazaki, S., Ishikawa, H. and Fujiwara, H: Structural analysis of TRAS1, a novel family of telomeric repeat associated retrotransposons in the silkworm, Bombyx mori. Mol. Cell. Biol. (1995) 15, 4545-4552.

7) Takahashi, H., Okazaki, S. and Fujiwara, H.: A new family of site-specific retrotransposons, SART1, is inserted into telomeric repeats of the silkworm, Bombyx mori.. Nucleic Acids Res. (1997) 25, 1578-1584.

8) Takahashi, H. and Fujiwara, H.: Transcription analysis of the telomeric repeat-specific retrotransposons TRAS1 and SART1 of the silkworm Bombyx mori. Nucleic Acids Res. (1999) 27, 2015-2021.

9) Sasaki, T. and Fujiwara, H.: Detection and distribution patterns of telomerase activity in insects. Eur. J. Biochem. (2000) 267, 3025-3031.

10) Fujiwara, H., Nakazato, Y., Okazaki, S. and Ninaki, O.: Stability and telomere structure of chromosomal fragments in two different mosaic strains of the silkworm, Bombyx mori. Zool Sci. (2000) 17, 743-750.

11) Anzai, T., Takahashi, H. and Fujiwara, H.: Sequence-specific recognition and cleavage of telomeric repeat (TTAGG)n by endonuclease of non-LTR retrotransposon, TRAS1. Mol Cell. Biol. (2001) 21, 100-108.

12) Kubo, Y., Okazaki, S., Anzai, T. and Fujiwara, H.: Structural and phylogenetic analysis of TRAS, telomeric repeat-specific non-LTR retrotransposon families in lepidopteran insects. Mol. Biol. Evol, (2001) 18. 848-857.

13) Kojima, K, Kubo, Y. and Fujiwara, H.: Complex and tandem repeat structure in sub-telomere of crickets, T. taiwanemma. J. Mol. Evol, (2002) 54, 474-485.

14) Takahashi, H. and Fujiwara, H.: Transplantation of target site specificity by swapping endonuclease domains of two LINEs. EMBO. J. (2002) 21, 408-417.

15) Kojima, K. K. and Fujiwara, H.: Evolution of target specificity in R1 clade non-LTR retrotransposons. Mol. Biol. Evol, (2003) 20, 351-361.

16) Kojima, K. K. and Fujiwara, H.: Cross-genome screening of novel sequence-specific non-LTR retrotransposons: various multicopy RNA genes and microsatellites are selected as targets. Mol. Biol. Evol. (2004) 21, 207-217.

17) Matsumoto, T., Takahashi, H. and Fujiwara, H. Targeted nuclear import of ORF1 protein is required for in vivo retrotransposition of telomere-specific non-long terminal repeat retrotransposon, SART1. Mol. Cell Biol. (2004) 24, 105-122.

18) Osanai, M., Takahashi, H., Kojima, K. K., Hamada, M. and Fujiwara, H.: Novel motifs in 3’-untranslated region required for precise reverse transcription start of telomere specific LINE, SART1. Mol. Cell Biol. (2004) 24, 7902-7913.

19) Maita, N., Anzai, T., Aoyagi, H., Mizuno, H. and Fujiwara, H.: Crystal structure of the endonuclease domain encoded by the telomere-specific LINE, TRAS1. J. Biol. Chem (2004) 279, 41067-41076.

20) Anzai T., Osanai, M., Hamada, M. and Fujiwara, H.: Functional roles of read-through 28S rRNA sequence in in vivo retrotransposition of non-LTR retrotransposon, R1Bm. Nucleic Acids Res. (2005) 33, 1993-2002.

21) Fujiwara, H., Osanai, M., Matsumoto, T. and Kojima, K. K.: (Review article) Telomere-specific non-LTR retrotransposons and telomere maintenance in the silkworm, Bombyx mori” Chromosome Research 13, 455-467 (2005).

22) Kojima, K. K. and Fujiwara, H.: An extraordinary retrotransposon family encoding dual endonucleases, Genome Research, in press (2005).

23) Kojima, K. K. Matsumoto, T. and Fujiwara, H.: Eukaryotic translation coupling in UAAUG stop-start codons for the bicystronic RNA translation of non-LTR retrotransposon SART1. Mol. Cell Biol 25, 7675-7686. (2005)

24) Kojima, K. K. and Fujiwara, H.: Long-term inheritance of the 28S rDNA-specific retrotransposon R2, Mol. Biol. Evol. 22, 2157-2165 (2005)

25) Matsumoto, T. Hamada, M. Osanai, M. and Fujiwara, H.: Essential domains for Ribonucleoprotein complex formation required for retrotransposition of a telomere specific non-LTR retrotransposon SART1. Mol. Cell. Biol. 26, 5168-5179 (2006)

26) Osanai, M., Kojima, K. K., Futahashi, R., Yaguchi, S. and Fujiwara, H.: Identification and characterization of the telomerase reverse transcriptase of Bombyx mori (silkworm) and Tribolium castaneum (flour beetle). Gene 376, 281-289 (2006)

27) Kojima KK. Kuma, K., Toh, H. and Fujiwara, H.: Identification of rDNA-specific non-LTR retrotransposons in Cnidaria. Molecular Biology and Evolution, 23, 1984－1994 (2006)

28) Osanai-Futahashi, M., Suetsugu, Y., Mita, K. and Fujiwara, H.: Genome-wide screening and characterization of transposable elements and their distribution analysis in the silkworm, Bombyx mori. Insect Biochem. Mol. Biol. 38, 1046-1146 (2008)

29) Yoshitake, K., Aoyagi, H. and Fujiwara, H.: Creation of a novel telomere-cutting endonuclease based on the EN domain of telomere-specific non-LTR retrotransposon, TRAS1. Mobile DNA, 1, 13 (open access) (2010)

30) Mitchell, M., Gillis, A., Futahashi, M., Fujiwara, H. and Skordalakes, E.: Structural basis for telomerase catalytic subunit TERT binding to RNA template and telomeric DNA. Nature Structural and Molecular Biology, 17: 513-518 (2010)

31) Osanai-Futahashi, M. and Fujiwara, H.: Coevolution of telomeric repeats and telomeric-repeat-specific non-LTR retrotransposons in insects. Molecular Biology and Evolution. 28, 2983-2986 (2011)

32) Fujiwara, H.: Accumulation of Telomeric-Repeat-Specific Retrotransposons in Subtelomere of Bombyx mori and Tribolium castaneum. Capter 13 in “Subtelomeres” eds. by E. J. Louis & M. M. Becker, 227-241, Springer (2014)

33) Fujiwara, H.: Site-specific non-LTR retrotransposons. Chapter 50 in “Mobile DNA III” eds. by N. Craig et al., pp1147-1163. doi: 10.1128/9781555819217 (2015) 2015.8/25

34) Fujiwara, H.: Site-specific non-LTR retrotransposons. Microbiology Spectrum, 3(2). April doi: 10.1128/microbiolspec.MDNA3-0001-2014 (2015)

35) Kojima, K. Seto, Y., Fujiwara, H.: The wide distribution and change of target specificity of R2 non-LTR retrotransposons in animals. PLoS One, e0163496 (2016)

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