ENST00000534336.1

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Annotated Information

Transcriptomic Nomeclature

hsa-N11QT0096001-SSCY-LMXXX01 Help

Name

Malat1: Metastasis-associated lung adenocarcinoma transcript 1

Neat2: Nuclear enriched abundant transcript 2

Characteristics

Malat1 gene is localized in the intergenic region of the genome. It is about 8kb in length and the transcript has only one exon [1][2]. The 3’-end of the transcript is a conserved tRNA-like sequence, which can be modified by RNase P and cleaved by RNase Z to yield another ncRNA (61nt), the cytoplasmic MALAT1-associated small cytoplasmic RNA (mascRNA) [3].

Malat1 is stable in human B cells (half-life: 16.5 h) [4] and Hela cells (half-life: about 7 h) [5], but is unstable in mouse 3T3 cells (half-life: 3 h) [4] and N2A cells ( half-life: 4 h) [4]. MALAT-1 is generally stable in cancer cells, with the half-life ranging from ~ 9 h to > 12 h in various cancer cells [6]. Xrn2, PM/Scl-75, PARN, and Mtr4, known nuclear RNases or RNA helicases, do not affect MALAT-1 degradation [6].

Cellular localization

MALAT-1 localizes predominately in the nucleus [2]. In G2/M cell cycle phase, MALAT-1 transcripts partially translocate from the nucleus into the cytoplasm [7]. RNPS1, SRm160, and IBP160 are found to contribute to the nuclear localization of MALAT-1 [8].

Function

Figure 1. Hypothetical model depicting the role of MALAT1 in AS (alternative splicing) regulation. (Ea) In normal cells, MALAT1, by associating with SR proteins in nuclear speckles and in the nucleoplasm, regulates their recruitment to the pre-mRNA, thereby regulating AS. Here we have shown SAT1 pre-mRNA as an example that undergoes alternate exon exclusion in normal cells. However, in MALAT1-depleted cells (Eb), cellular levels of SR proteins are increased and are also present predominantly in the dephosphorylated form, resulting in changes in AS of pre-mRNA. In case of SAT1 pre-mRNA, MALAT1 depletion results in the inclusion of an alternative exon containing weak splice sites. (from reference [9]).

MALAT-1 localizes specifically in the SC35 splicing domains in the nucleus, suggesting its function in pre-mRNA metabolism or specific nuclear structures [2]. The later studies found that MALAT-1 could modulate mRNA alternative splicing via its interaction with the serine/arginine-rich (SR) family of nuclear phosphoproteins that are involved in the splicing machinery [9]. MALAT-1 regulates synapse formation by modulating the expression of genes involved in synapse formation and/or maintenance [10]. However, splicing alterations were not found after Malat1 ablation in mice [11]. Also, MALAT1 does not alter alternative splicing but actively regulates gene expression including a set of metastasis-associated genes in lung cancer cells [12]. These results indicate that alternative functions for MALAT-1 may exist.

MALAT-1 can function by participating in localization of important proteins, such as hnRNP C [7] and growth control genes [13]. MALAT-1 is found to regulate cell cycle progress in G2/M phase [7][9], G1/S phase [14], and G0/G1 phase [15]. In the G2/M phase, MALAT-1 interacts with hnRNP C to facilitate the cytoplasmic translocation of hnRNP C, leading to cell cycle progresion [7]. MALAT1 could interact with the demethylated form of CBX4 (chromobox homolog 4), and controls the relocalization of growth control genes between polycomb bodies and interchromatin granules [13]. MALAT1 could bind to Human PSF (hPSF) protein to release hPSF from a repressed proto-oncogene and activate transcription, driving transformation and tumorigenesis [16].

MALAT-1 regulates synaptogenesis [10]and is involved in the development of advanced invasive placentation [17]. Deregulation of MALAT-1 is found to be closely associated with the development of cancer. In vitro, it is found that MALAT-1 promotes epithelial–mesenchymal transition (EMT) of bladder cancer cells by activating Wnt signaling [18]. 3' end of MALAT-1 (6918 nt-8441 nt) is found to be important in colorectal cancer metastasis [19]. In lung adenocarcinoma cells, MALAT-1 may regulate cell motility through transcriptional and post-transcriptional regulation of motility related gene expression [20]. However, mechanisms of these functions are not clear.

Expression

MALAT-1 is ubiquity expressed in various normal tissues [1][2][3][10], but the expression levels are quite different among tissues [1][2][10].

MALAT-1 is over-expressed in many human carcinomas, including those of the breast, pancreas, lung, colon, prostate, and liver [21].

It is also found to be up-regulated in the cerebellum, hippocampus and brain stem of human alcoholics [22].

Primer Forward primer Reverse primer
RT-PCR 5'-AAAGCAAGGTCTCCCCACAAG-3' 5'-GGTCTGTGCTAGATCAAAAGGCA-3'[23][24]
5'-CTTCCCTAGGGGATTTCAGG-3' 5'-GCCCACAGGAACAAGTCCTA-3'[15]
5'-GAATTGCGTCATTTAAAGCCTAGTT-3' 5'-GTTTCATCCTACCACTCCCAATTAAT-3'[25]
5'-cggaagtaattcaagatcaagag-3' 5'-actgaatccacttctgtgtagc-3'[16]
cDNA amplication 5'-GTAGGGCCCTCCATGGCGATTTGCCTTGTGAGCAC-3' 5'-GAGCTCGAGGTCCTGAAGACAGATTAGTAGTCAAAGC-3'[6]
Northern blot 5'-GGCAGGAGAGACAACAAAGC-3' 5'-CTCGACACCATCGTTACCT-3'[2]

Regulation

In breast cancer cells, high concentration E2 treatment largely decreases MALAT-1 RNA level in an ERa independent way [26].

Disruption of p53 appears to play an important role in the up-regulation of MALAT-1 [27].

CREB (cyclic AMP-responsive element binding) transcription factor is found to bind to the defined proximal promoter of the MALAT1 gene, leading to the up-regulation of MALAT1 [28].

Diseases

MALAT-1 was first identified as a prognostic marker for metastasis and patient survival in non-small cell lung cancer (NSCLC) [29]. It is found to be overexpressed in various tumors and cancer cell lines, including lung cancer [1][21][29], endometrial stromal sarcoma of the uterus [30], hepatocellular carcinomas [21][31], breast cancer [21][32], pancreas cancer [21], colon cancer [21], prostate cancer [15][21], melanoma [23], bladder cancer [18]. Overexpression of MALAT-1 in cancer cells is closely associated with tumor growth and metastasis [12][20][23][29].

There is no significant difference in MALAT-1 lncRNA levels in normal pituitary tissues, invasive NFPAs (non-functioning pituitary adenomas), and non-invasive NFPAs, and no significant association between MALAT-1 expression and patient clinicopathological characteristics [24].

Evolution

MALAT-1 is highly conserved across mammals [10]. However, sequence conservation is limited in vertebrates. Sequence similarity between zebrafish and mammalian MALAT1 is restricted to the 3′ end, while the length of MALAT1 (~7 kb) along with the gene structure appeare to be roughly fixed in all vertebrates [14].

Associated components

hnRNP C [7]

CBX4 (chromobox homolog 4) [13]

Human PSF (hPSF) protein [16]


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Labs working on this lncRNA

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References

  1. ↑ 1.0 1.1 1.2 1.3 Ji, P., Diederichs, S., Wang, W., Boing, S., Metzger, R., Schneider, P.M., Tidow, N., Brandt, B., Buerger, H., Bulk, E. et al. (2003) MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene, 22, 8031-8041.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Hutchinson, J.N., Ensminger, A.W., Clemson, C.M., Lynch, C.R., Lawrence, J.B. and Chess, A. (2007) A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genomics, 8, 39.
  3. ↑ 3.0 3.1 Wilusz, J.E., Freier, S.M. and Spector, D.L. (2008) 3' end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell, 135, 919-932.
  4. ↑ 4.0 4.1 4.2 Clark, M.B., Johnston, R.L., Inostroza-Ponta, M., Fox, A.H., Fortini, E., Moscato, P., Dinger, M.E. and Mattick, J.S. (2012) Genome-wide analysis of long noncoding RNA stability. Genome Res, 22, 885-898.
  5. ↑ Tani, H., Mizutani, R., Salam, K.A., Tano, K., Ijiri, K., Wakamatsu, A., Isogai, T., Suzuki, Y. and Akimitsu, N. (2012) Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals. Genome Res, 22, 947-956.
  6. ↑ 6.0 6.1 6.2 Tani, H., Nakamura, Y., Ijiri, K. and Akimitsu, N. (2010) Stability of MALAT-1, a nuclear long non-coding RNA in mammalian cells, varies in various cancer cells. Drug Discov Ther, 4, 235-239.
  7. ↑ 7.0 7.1 7.2 7.3 7.4 Yang, F., Yi, F., Han, X., Du, Q. and Liang, Z. (2013) MALAT-1 interacts with hnRNP C in cell cycle regulation. FEBS Lett, 587, 3175-3181.
  8. ↑ Miyagawa, R., Tano, K., Mizuno, R., Nakamura, Y., Ijiri, K., Rakwal, R., Shibato, J., Masuo, Y., Mayeda, A., Hirose, T. et al. (2012) Identification of cis- and trans-acting factors involved in the localization of MALAT-1 noncoding RNA to nuclear speckles. RNA, 18, 738-751.
  9. ↑ 9.0 9.1 9.2 Tripathi, V., Ellis, J.D., Shen, Z., Song, D.Y., Pan, Q., Watt, A.T., Freier, S.M., Bennett, C.F., Sharma, A., Bubulya, P.A. et al. (2010) The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell, 39, 925-938.
  10. ↑ 10.0 10.1 10.2 10.3 10.4 Bernard, D., Prasanth, K.V., Tripathi, V., Colasse, S., Nakamura, T., Xuan, Z., Zhang, M.Q., Sedel, F., Jourdren, L., Coulpier, F. et al. (2010) A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression. EMBO J, 29, 3082-3093.
  11. ↑ Zhang, B., Arun, G., Mao, Y.S., Lazar, Z., Hung, G., Bhattacharjee, G., Xiao, X., Booth, C.J., Wu, J., Zhang, C. et al. (2012) The lncRNA Malat1 is dispensable for mouse development but its transcription plays a cis-regulatory role in the adult. Cell Rep, 2, 111-123.
  12. ↑ 12.0 12.1 Gutschner, T., Hammerle, M., Eissmann, M., Hsu, J., Kim, Y., Hung, G., Revenko, A., Arun, G., Stentrup, M., Gross, M. et al. (2013) The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res, 73, 1180-1189.
  13. ↑ 13.0 13.1 13.2 Yang, L., Lin, C., Liu, W., Zhang, J., Ohgi, K.A., Grinstein, J.D., Dorrestein, P.C. and Rosenfeld, M.G. (2011) ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell, 147, 773-788.
  14. ↑ 14.0 14.1 Ulitsky, I., Shkumatava, A., Jan, C.H., Sive, H. and Bartel, D.P. (2011) Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell, 147, 1537-1550.
  15. ↑ 15.0 15.1 15.2 Ren, S., Liu, Y., Xu, W., Sun, Y., Lu, J., Wang, F., Wei, M., Shen, J., Hou, J., Gao, X. et al. (2013) Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer. J Urol, 190, 2278-2287.
  16. ↑ 16.0 16.1 16.2 Li, L., Feng, T., Lian, Y., Zhang, G., Garen, A. and Song, X. (2009) Role of human noncoding RNAs in the control of tumorigenesis. Proc Natl Acad Sci U S A, 106, 12956-12961.
  17. ↑ Tseng, J.J., Hsieh, Y.T., Hsu, S.L. and Chou, M.M. (2009) Metastasis associated lung adenocarcinoma transcript 1 is up-regulated in placenta previa increta/percreta and strongly associated with trophoblast-like cell invasion in vitro. Mol Hum Reprod, 15, 725-731.
  18. ↑ 18.0 18.1 Ying, L., Chen, Q., Wang, Y., Zhou, Z., Huang, Y. and Qiu, F. (2012) Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition. Mol Biosyst, 8, 2289-2294.
  19. ↑ Xu, C., Yang, M., Tian, J., Wang, X. and Li, Z. (2011) MALAT-1: a long non-coding RNA and its important 3' end functional motif in colorectal cancer metastasis. Int J Oncol, 39, 169-175.
  20. ↑ 20.0 20.1 Tano, K., Mizuno, R., Okada, T., Rakwal, R., Shibato, J., Masuo, Y., Ijiri, K. and Akimitsu, N. (2010) MALAT-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes. FEBS Lett, 584, 4575-4580.
  21. ↑ 21.0 21.1 21.2 21.3 21.4 21.5 21.6 Lin, R., Maeda, S., Liu, C., Karin, M. and Edgington, T.S. (2007) A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene, 26, 851-858.
  22. ↑ Kryger, R., Fan, L., Wilce, P.A. and Jaquet, V. (2012) MALAT-1, a non protein-coding RNA is upregulated in the cerebellum, hippocampus and brain stem of human alcoholics. Alcohol, 46, 629-634.
  23. ↑ 23.0 23.1 23.2 Tian, Y., Zhang, X., Hao, Y., Fang, Z. and He, Y. (2014) Potential roles of abnormally expressed long noncoding RNA UCA1 and Malat-1 in metastasis of melanoma. Melanoma Res.
  24. ↑ 24.0 24.1 Li, Z., Li, C., Liu, C., Yu, S. and Zhang, Y. (2014) Expression of the long non-coding RNAs MEG3, HOTAIR, and MALAT-1 in non-functioning pituitary adenomas and their relationship to tumor behavior. Pituitary.
  25. ↑ Guo, F., Li, Y., Liu, Y., Wang, J. and Li, G. (2010) Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaSki human cervical cancer cells suppresses cell proliferation and invasion. Acta Biochim Biophys Sin (Shanghai), 42, 224-229.
  26. ↑ Zhao, Z., Chen, C., Liu, Y. and Wu, C. (2014) 17beta-Estradiol treatment inhibits breast cell proliferation, migration and invasion by decreasing MALAT-1 RNA level. Biochem Biophys Res Commun, 445, 388-393.
  27. ↑ Jeffers, L.K., Duan, K., Ellies, L.G., Seaman, W.T., Burger-Calderon, R.A., Diatchenko, L.B. and Webster-Cyriaque, J. (2013) Correlation of transcription of MALAT-1, a novel noncoding RNA, with deregulated expression of tumor suppressor p53 in small DNA tumor virus models. J Cancer Ther, 4.
  28. ↑ Koshimizu, T.A., Fujiwara, Y., Sakai, N., Shibata, K. and Tsuchiya, H. (2010) Oxytocin stimulates expression of a noncoding RNA tumor marker in a human neuroblastoma cell line. Life Sci, 86, 455-460.
  29. ↑ 29.0 29.1 29.2 Schmidt, L.H., Spieker, T., Koschmieder, S., Schaffers, S., Humberg, J., Jungen, D., Bulk, E., Hascher, A., Wittmer, D., Marra, A. et al. (2011) The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. J Thorac Oncol, 6, 1984-1992.
  30. ↑ Yamada, K., Kano, J., Tsunoda, H., Yoshikawa, H., Okubo, C., Ishiyama, T. and Noguchi, M. (2006) Phenotypic characterization of endometrial stromal sarcoma of the uterus. Cancer Sci, 97, 106-112.
  31. ↑ Lai, M.C., Yang, Z., Zhou, L., Zhu, Q.Q., Xie, H.Y., Zhang, F., Wu, L.M., Chen, L.M. and Zheng, S.S. (2011) Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation. Med Oncol, 29, 1810-1816.
  32. ↑ Guffanti, A., Iacono, M., Pelucchi, P., Kim, N., Solda, G., Croft, L.J., Taft, R.J., Rizzi, E., Askarian-Amiri, M., Bonnal, R.J. et al. (2009) A transcriptional sketch of a primary human breast cancer by 454 deep sequencing. BMC Genomics, 10, 163.


Basic Information

Transcript ID

ENST00000534336.1

Source

{{{source}}}

Same with

lnc-SCYL1-1:2;n343070;Malat1(NR_002819.2)

Classification

intergenic

Length

{{{length}}}

Genomic location

chr11+:65265233-65273940

Exon number

{{{number}}}

Exons

{{{exons}}}

Genome context

{{{context}}}

Sequence
000001 GTAAAGGACT GGGGCCCCGC AACTGGCCTC TCCTGCCCTC TTAAGCGCAG CGCCATTTTA GCAACGCAGA AGCCCGGCGC 000080
000081 CGGGAAGCCT CAGCTCGCCT GAAGGCAGGT CCCCTCTGAC GCCTCCGGGA GCCCAGGTTT CCCAGAGTCC TTGGGACGCA 000160
000161 GCGACGAGTT GTGCTGCTAT CTTAGCTGTC CTTATAGGCT GGCCATTCCA GGTGGTGGTA TTTAGATAAA ACCACTCAAA 000240
000241 CTCTGCAGTT TGGTCTTGGG GTTTGGAGGA AAGCTTTTAT TTTTCTTCCT GCTCCGGTTC AGAAGGTCTG AAGCTCATAC 000320
000321 CTAACCAGGC ATAACACAGA ATCTGCAAAA CAAAAACCCC TAAAAAAGCA GACCCAGAGC AGTGTAAACA CTTCTGGGTG 000400
000401 TGTCCCTGAC TGGCTGCCCA AGGTCTCTGT GTCTTCGGAG ACAAAGCCAT TCGCTTAGTT GGTCTACTTT AAAAGGCCAC 000480
000481 TTGAACTCGC TTTCCATGGC GATTTGCCTT GTGAGCACTT TCAGGAGAGC CTGGAAGCTG AAAAACGGTA GAAAAATTTC 000560
000561 CGTGCGGGCC GTGGGGGGCT GGCGGCAACT GGGGGGCCGC AGATCAGAGT GGGCCACTGG CAGCCAACGG CCCCCGGGGC 000640
000641 TCAGGCGGGG AGCAGCTCTG TGGTGTGGGA TTGAGGCGTT TTCCAAGAGT GGGTTTTCAC GTTTCTAAGA TTTCCCAAGC 000720
000721 AGACAGCCCG TGCTGCTCCG ATTTCTCGAA CAAAAAAGCA AAACGTGTGG CTGTCTTGGG AGCAAGTCGC AGGACTGCAA 000800
000801 GCAGTTGGGG GAGAAAGTCC GCCATTTTGC CACTTCTCAA CCGTCCCTGC AAGGCTGGGG CTCAGTTGCG TAATGGAAAG 000880
000881 TAAAGCCCTG AACTATCACA CTTTAATCTT CCTTCAAAAG GTGGTAAACT ATACCTACTG TCCCTCAAGA GAACACAAGA 000960
000961 AGTGCTTTAA GAGGTATTTT AAAAGTTCCG GGGGTTTTGT GAGGTGTTTG ATGACCCGTT TAAAATATGA TTTCCATGTT 001040
001041 TCTTTTGTCT AAAGTTTGCA GCTCAAATCT TTCCACACGC TAGTAATTTA AGTATTTCTG CATGTGTAGT TTGCATTCAA 001120
001121 GTTCCATAAG CTGTTAAGAA AAATCTAGAA AAGTAAAACT AGAACCTATT TTTAACCGAA GAACTACTTT TTGCCTCCCT 001200
001201 CACAAAGGCG GCGGAAGGTG ATCGAATTCC GGTGATGCGA GTTGTTCTCC GTCTATAAAT ACGCCTCGCC CGAGCTGTGC 001280
001281 GGTAGGCATT GAGGCAGCCA GCGCAGGGGC TTCTGCTGAG GGGGCAGGCG GAGCTTGAGG AAACCGCAGA TAAGTTTTTT 001360
001361 TCTCTTTGAA AGATAGAGAT TAATACAACT ACTTAAAAAA TATAGTCAAT AGGTTACTAA GATATTGCTT AGCGTTAAGT 001440
001441 TTTTAACGTA ATTTTAATAG CTTAAGATTT TAAGAGAAAA TATGAAGACT TAGAAGAGTA GCATGAGGAA GGAAAAGATA 001520
001521 AAAGGTTTCT AAAACATGAC GGAGGTTGAG ATGAAGCTTC TTCATGGAGT AAAAAATGTA TTTAAAAGAA AATTGAGAGA 001600
001601 AAGGACTACA GAGCCCCGAA TTAATACCAA TAGAAGGGCA ATGCTTTTAG ATTAAAATGA AGGTGACTTA AACAGCTTAA 001680
001681 AGTTTAGTTT AAAAGTTGTA GGTGATTAAA ATAATTTGAA GGCGATCTTT TAAAAAGAGA TTAAACCGAA GGTGATTAAA 001760
001761 AGACCTTGAA ATCCATGACG CAGGGAGAAT TGCGTCATTT AAAGCCTAGT TAACGCATTT ACTAAACGCA GACGAAAATG 001840
001841 GAAAGATTAA TTGGGAGTGG TAGGATGAAA CAATTTGGAG AAGATAGAAG TTTGAAGTGG AAAACTGGAA GACAGAAGTA 001920
001921 CGGGAAGGCG AAGAAAAGAA TAGAGAAGAT AGGGAAATTA GAAGATAAAA ACATACTTTT AGAAGAAAAA AGATAAATTT 002000
002001 AAACCTGAAA AGTAGGAAGC AGAAGAAAAA AGACAAGCTA GGAAACAAAA AGCTAAGGGC AAAATGTACA AACTTAGAAG 002080
002081 AAAATTGGAA GATAGAAACA AGATAGAAAA TGAAAATATT GTCAAGAGTT TCAGATAGAA AATGAAAAAC AAGCTAAGAC 002160
002161 AAGTATTGGA GAAGTATAGA AGATAGAAAA ATATAAAGCC AAAAATTGGA TAAAATAGCA CTGAAAAAAT GAGGAAATTA 002240
002241 TTGGTAACCA ATTTATTTTA AAAGCCCATC AATTTAATTT CTGGTGGTGC AGAAGTTAGA AGGTAAAGCT TGAGAAGATG 002320
002321 AGGGTGTTTA CGTAGACCAG AACCAATTTA GAAGAATACT TGAAGCTAGA AGGGGAAGTT GGTTAAAAAT CACATCAAAA 002400
002401 AGCTACTAAA AGGACTGGTG TAATTTAAAA AAAACTAAGG CAGAAGGCTT TTGGAAGAGT TAGAAGAATT TGGAAGGCCT 002480
002481 TAAATATAGT AGCTTAGTTT GAAAAATGTG AAGGACTTTC GTAACGGAAG TAATTCAAGA TCAAGAGTAA TTACCAACTT 002560
002561 AATGTTTTTG CATTGGACTT TGAGTTAAGA TTATTTTTTA AATCCTGAGG ACTAGCATTA ATTGACAGCT GACCCAGGTG 002640
002641 CTACACAGAA GTGGATTCAG TGAATCTAGG AAGACAGCAG CAGACAGGAT TCCAGGAACC AGTGTTTGAT GAAGCTAGGA 002720
002721 CTGAGGAGCA AGCGAGCAAG CAGCAGTTCG TGGTGAAGAT AGGAAAAGAG TCCAGGAGCC AGTGCGATTT GGTGAAGGAA 002800
002801 GCTAGGAAGA AGGAAGGAGC GCTAACGATT TGGTGGTGAA GCTAGGAAAA AGGATTCCAG GAAGGAGCGA GTGCAATTTG 002880
002881 GTGATGAAGG TAGCAGGCGG CTTGGCTTGG CAACCACACG GAGGAGGCGA GCAGGCGTTG TGCGTAGAGG ATCCTAGACC 002960
002961 AGCATGCCAG TGTGCCAAGG CCACAGGGAA AGCGAGTGGT TGGTAAAAAT CCGTGAGGTC GGCAATATGT TGTTTTTCTG 003040
003041 GAACTTACTT ATGGTAACCT TTTATTTATT TTCTAATATA ATGGGGGAGT TTCGTACTGA GGTGTAAAGG GATTTATATG 003120
003121 GGGACGTAGG CCGATTTCCG GGTGTTGTAG GTTTCTCTTT TTCAGGCTTA TACTCATGAA TCTTGTCTGA AGCTTTTGAG 003200
003201 GGCAGACTGC CAAGTCCTGG AGAAATAGTA GATGGCAAGT TTGTGGGTTT TTTTTTTTTA CACGAATTTG AGGAAAACCA 003280
003281 AATGAATTTG ATAGCCAAAT TGAGACAATT TCAGCAAATC TGTAAGCAGT TTGTATGTTT AGTTGGGGTA ATGAAGTATT 003360
003361 TCAGTTTTGT GAATAGATGA CCTGTTTTTA CTTCCTCACC CTGAATTCGT TTTGTAAATG TAGAGTTTGG ATGTGTAACT 003440
003441 GAGGCGGGGG GGAGTTTTCA GTATTTTTTT TTGTGGGGGT GGGGGCAAAA TATGTTTTCA GTTCTTTTTC CCTTAGGTCT 003520
003521 GTCTAGAATC CTAAAGGCAA ATGACTCAAG GTGTAACAGA AAACAAGAAA ATCCAATATC AGGATAATCA GACCACCACA 003600
003601 GGTTTACAGT TTATAGAAAC TAGAGCAGTT CTCACGTTGA GGTCTGTGGA AGAGATGTCC ATTGGAGAAA TGGCTGGTAG 003680
003681 TTACTCTTTT TTCCCCCCAC CCCCTTAATC AGACTTTAAA AGTGCTTAAC CCCTTAAACT TGTTATTTTT TACTTGAAGC 003760
003761 ATTTTGGGAT GGTCTTAACA GGGAAGAGAG AGGGTGGGGG AGAAAATGTT TTTTTCTAAG ATTTTCCACA GATGCTATAG 003840
003841 TACTATTGAC AAACTGGGTT AGAGAAGGAG TGTACCGCTG TGCTGTTGGC ACGAACACCT TCAGGGACTG GAGCTGCTTT 003920
003921 TATCCTTGGA AGAGTATTCC CAGTTGAAGC TGAAAAGTAC AGCACAGTGC AGCTTTGGTT CATATTCAGT CATCTCAGGA 004000
004001 GAACTTCAGA AGAGCTTGAG TAGGCCAAAT GTTGAAGTTA AGTTTTCCAA TAATGTGACT TCTTAAAAGT TTTATTAAAG 004080
004081 GGGAGGGGCA AATATTGGCA ATTAGTTGGC AGTGGCCTGT TACGGTTGGG ATTGGTGGGG TGGGTTTAGG TAATTGTTTA 004160
004161 GTTTATGATT GCAGATAAAC TCATGCCAGA GAACTTAAAG TCTTAGAATG GAAAAAGTAA AGAAATATCA ACTTCCAAGT 004240
004241 TGGCAAGTAA CTCCCAATGA TTTAGTTTTT TTCCCCCCAG TTTGAATTGG GAAGCTGGGG GAAGTTAAAT ATGAGCCACT 004320
004321 GGGTGTACCA GTGCATTAAT TTGGGCAAGG AAAGTGTCAT AATTTGATAC TGTATCTGTT TTCCTTCAAA GTATAGAGCT 004400
004401 TTTGGGGAAG GAAAGTATTG AACTGGGGGT TGGTCTGGCC TACTGGGCTG ACATTAACTA CAATTATGGG AAATGCAAAA 004480
004481 GTTGTTTGGA TATGGTAGTG TGTGGTTCTC TTTTGGAATT TTTTTCAGGT GATTTAATAA TAATTTAAAA CTACTATAGA 004560
004561 AACTGCAGAG CAAAGGAAGT GGCTTAATGA TCCTGAAGGG ATTTCTTCTG ATGGTAGCTT TTGTATTATC AAGTAAGATT 004640
004641 CTATTTTCAG TTGTGTGTAA GCAAGTTTTT TTTTAGTGTA GGAGAAATAC TTTTCCATTG TTTAACTGCA AAACAAGATG 004720
004721 TTAAGGTATG CTTCAAAAAT TTTGTAAATT GTTTATTTTA AACTTATCTG TTTGTAAATT GTAACTGATT AAGAATTGTG 004800
004801 ATAGTTCAGC TTGAATGTCT CTTAGAGGGT GGGCTTTTGT TGATGAGGGA GGGGAAACTT TTTTTTTTTC TATAGACTTT 004880
004881 TTTCAGATAA CATCTTCTGA GTCATAACCA GCCTGGCAGT ATGATGGCCT AGATGCAGAG AAAACAGCTC CTTGGTGAAT 004960
004961 TGATAAGTAA AGGCAGAAAA GATTATATGT CATACCTCCA TTGGGGAATA AGCATAACCC TGAGATTCTT ACTACTGATG 005040
005041 AGAACATTAT CTGCATATGC CAAAAAATTT TAAGCAAATG AAAGCTACCA ATTTAAAGTT ACGGAATCTA CCATTTTAAA 005120
005121 GTTAATTGCT TGTCAAGCTA TAACCACAAA AATAATGAAT TGATGAGAAA TACAATGAAG AGGCAATGTC CATCTCAAAA 005200
005201 TACTGCTTTT ACAAAAGCAG AATAAAAGCG AAAAGAAATG AAAATGTTAC ACTACATTAA TCCTGGAATA AAAGAAGCCG 005280
005281 AAATAAATGA GAGATGAGTT GGGATCAAGT GGATTGAGGA GGCTGTGCTG TGTGCCAATG TTTCGTTTGC CTCAGACAGG 005360
005361 TATCTCTTCG TTATCAGAAG AGTTGCTTCA TTTCATCTGG GAGCAGAAAA CAGCAGGCAG CTGTTAACAG ATAAGTTTAA 005440
005441 CTTGCATCTG CAGTATTGCA TGTTAGGGAT AAGTGCTTAT TTTTAAGAGC TGTGGAGTTC TTAAATATCA ACCATGGCAC 005520
005521 TTTCTCCTGA CCCCTTCCCT AGGGGATTTC AGGATTGAGA AATTTTTCCA TCGAGCCTTT TTAAAATTGT AGGACTTGTT 005600
005601 CCTGTGGGCT TCAGTGATGG GATAGTACAC TTCACTCAGA GGCATTTGCA TCTTTAAATA ATTTCTTAAA AGCCTCTAAA 005680
005681 GTGATCAGTG CCTTGATGCC AACTAAGGAA ATTTGTTTAG CATTGAATCT CTGAAGGCTC TATGAAAGGA ATAGCATGAT 005760
005761 GTGCTGTTAG AATCAGATGT TACTGCTAAA ATTTACATGT TGTGATGTAA ATTGTGTAGA AAACCATTAA ATCATTCAAA 005840
005841 ATAATAAACT ATTTTTATTA GAGAATGTAT ACTTTTAGAA AGCTGTCTCC TTATTTAAAT AAAATAGTGT TTGTCTGTAG 005920
005921 TTCAGTGTTG GGGCAATCTT GGGGGGGATT CTTCTCTAAT CTTTCAGAAA CTTTGTCTGC GAACACTCTT TAATGGACCA 006000
006001 GATCAGGATT TGAGCGGAAG AACGAATGTA ACTTTAAGGC AGGAAAGACA AATTTTATTC TTCATAAAGT GATGAGCATA 006080
006081 TAATAATTCC AGGCACATGG CAATAGAGGC CCTCTAAATA AGGAATAAAT AACCTCTTAG ACAGGTGGGA GATTATGATC 006160
006161 AGAGTAAAAG GTAATTACAC ATTTTATTTC CAGAAAGTCA GGGGTCTATA AATTGACAGT GATTAGAGTA ATACTTTTTC 006240
006241 ACATTTCCAA AGTTTGCATG TTAACTTTAA ATGCTTACAA TCTTAGAGTG GTAGGCAATG TTTTACACTA TTGACCTTAT 006320
006321 ATAGGGAAGG GAGGGGGTGC CTGTGGGGTT TTAAAGAATT TTCCTTTGCA GAGGCATTTC ATCCTTCATG AAGCCATTCA 006400
006401 GGATTTTGAA TTGCATATGA GTGCTTGGCT CTTCCTTCTG TTCTAGTGAG TGTATGAGAC CTTGCAGTGA GTTTATCAGC 006480
006481 ATACTCAAAA TTTTTTTCCT GGAATTTGGA GGGATGGGAG GAGGGGGTGG GGCTTACTTG TTGTAGCTTT TTTTTTTTTT 006560
006561 ACAGACTTCA CAGAGAATGC AGTTGTCTTG ACTTCAGGTC TGTCTGTTCT GTTGGCAAGT AAATGCAGTA CTGTTCTGAT 006640
006641 CCCGCTGCTA TTAGAATGCA TTGTGAAACG ACTGGAGTAT GATTAAAAGT TGTGTTCCCC AATGCTTGGA GTAGTGATTG 006720
006721 TTGAAGGAAA AAATCCAGCT GAGTGATAAA GGCTGAGTGT TGAGGAAATT TCTGCAGTTT TAAGCAGTCG TATTTGTGAT 006800
006801 TGAAGCTGAG TACATTTTGC TGGTGTATTT TTAGGTAAAA TGCTTTTTGT TCATTTCTGG TGGTGGGAGG GGACTGAAGC 006880
006881 CTTTAGTCTT TTCCAGATGC AACCTTAAAA TCAGTGACAA GAAACATTCC AAACAAGCAA CAGTCTTCAA GAAATTAAAC 006960
006961 TGGCAAGTGG AAATGTTTAA ACAGTTCAGT GATCTTTAGT GCATTGTTTA TGTGTGGGTT TCTCTCTCCC CTCCCTTGGT 007040
007041 CTTAATTCTT ACATGCAGGA ACACTCAGCA GACACACGTA TGCGAAGGGC CAGAGAAGCC AGACCCAGTA AGAAAAAATA 007120
007121 GCCTATTTAC TTTAAATAAA CCAAACATTC CATTTTAAAT GTGGGGATTG GGAACCACTA GTTCTTTCAG ATGGTATTCT 007200
007201 TCAGACTATA GAAGGAGCTT CCAGTTGAAT TCACCAGTGG ACAAAATGAG GAAAACAGGT GAACAAGCTT TTTCTGTATT 007280
007281 TACATACAAA GTCAGATCAG TTATGGGACA ATAGTATTGA ATAGATTTCA GCTTTATGCT GGAGTAACTG GCATGTGAGC 007360
007361 AAACTGTGTT GGCGTGGGGG TGGAGGGGTG AGGTGGGCGC TAAGCCTTTT TTTAAGATTT TTCAGGTACC CCTCACTAAA 007440
007441 GGCACCGAAG GCTTAAAGTA GGACAACCAT GGAGCCTTCC TGTGGCAGGA GAGACAACAA AGCGCTATTA TCCTAAGGTC 007520
007521 AAGAGAAGTG TCAGCCTCAC CTGATTTTTA TTAGTAATGA GGACTTGCCT CAACTCCCTC TTTCTGGAGT GAAGCATCCG 007600
007601 AAGGAATGCT TGAAGTACCC CTGGGCTTCT CTTAACATTT AAGCAAGCTG TTTTTATAGC AGCTCTTAAT AATAAAGCCC 007680
007681 AAATCTCAAG CGGTGCTTGA AGGGGAGGGA AAGGGGGAAA GCGGGCAACC ACTTTTCCCT AGCTTTTCCA GAAGCCTGTT 007760
007761 AAAAGCAAGG TCTCCCCACA AGCAACTTCT CTGCCACATC GCCACCCCGT GCCTTTTGAT CTAGCACAGA CCCTTCACCC 007840
007841 CTCACCTCGA TGCAGCCAGT AGCTTGGATC CTTGTGGGCA TGATCCATAA TCGGTTTCAA GGTAACGATG GTGTCGAGGT 007920
007921 CTTTGGTGGG TTGAACTATG TTAGAAAAGG CCATTAATTT GCCTGCAAAT TGTTAACAGA AGGGTATTAA AACCACAGCT 008000
008001 AAGTAGCTCT ATT