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1. P Poly(A) Human Alu P ORF1 ORF2 Poly(A) L1 Computational data Transposable elements Occurrences Percent (%) Family Subfamily Alu 20 1.44 AluJ 171 12.35 AluS 244 17.62 ′ SINE MIR 250 18.05 FAM 2 0.14 Table. Distribution of transposable element family in region of transposable element exonization FRAM 18 1.30 Transposable elements Transposable elements Retroelement FLAM 37 2.67 fusion region within genes SINE Family LINE Family LTR Family DNA Family Others HAL 13 0.94 RNA intermediate CDS 619 280 85 76 1 L1HS 1 0.07 76 30 33 5 0 5 UTR ′ - LTR element + LTR element L1P 18 1.30 44 20 14 5 0 3 UTR ′ LINE Retroposon - env + env L1M 153 11.05 Retrotransposon L2 151 10.90 - RT + RT L3 25 1.81 LTR ORF1 ORF2 LTR SINE Yeast Ty1/copia/truncated HERVs MaLR 67 4.84 ERV1 40 2.89 LTR LTR LTR Human THE1 ERVL 27 1.95 ERVK 6 0.43 Retrovirus Charlie 9 0.65 LINE HSMAR2 2 0.14 LTR gag pol env LTR Kanga1 1 0.07 Full-length HERVs/exogenous retrovirus DNA MARNA 3 0.22 MER 61 4.40 Tigger 14 1.01 Zaphod2 1 0.07 Promoter region Others Charlie 1 0.07 Experimental data Supplying the Promoter or Enhancer 1 exon Transcription change Exonization in UTR and CDS region 2 exon 1 exon Alternative Promoter 2 exon 1 exon Alternative Polyadenylation last exon Identification of fusion transcripts with retroviral elements and its application as a cancer biomarker Yun-Ji Kim1, Jae-Won Huh2, Dae-Soo Kim3, Hong-Seok Ha1, Kung Ahn1, Ja-Rang Lee1, Yi-Deun Jung1, and Heui-Soo Kim1 1 Division of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea2 National Primate Research Center (NPRC), KRIBB, Ochang, Chungbuk 363-883, Republic of Korea 3 Korea Bioinformation Center, KRIBB, Daejeon 305-806, Korea http://www.primate.or.kr Abstract Results The human genome is estimated to be composed of 45% transposable elements (TEs). They have been reported to have capacity for affecting adjacent genes by altering transcriptional regulation. Most TEs are transcriptionally silent in normal tissues. However, TEs have been found to be expressed specifically in cancer cell lines. Here we investigated the cancer specific fusion transcript with TEs using bioinformatics and experimental approaches. To identify the candidate cancer markers, we adopted an analysis pipeline for screening methods to detect cancer-specific expression from expressed human sequences and developed a database. Total 999 genes fused with transposable elements were found to be cancer-specific in our analysis of the EST database. To confirm the candidate marker transcripts, experimental validation was conducted by RT-PCR analysis in tumor/adjacent normal tissues and corresponding cancer cell lines. Our results could contribute greatly to understand the human cancers in relation to transposable element.……..........................……...…... Table. Distribution of transposable element family in region of transposable element exonization Transposable elements Transposable elements fusion region within genes SINE Family LINE Family LTR Family DNA Family Others CDS 619 280 85 76 1 ′ 5 76 30 33 5 0 UTR ′ 3 44 20 14 5 0 UTR Introduction Aims Most of TEs are tranScr- iptionally silent in human normal tissues, however, some of TEs have been found to be expressed in placenta tissues and cancer cell lines. The L1 antisense promoter-driven transcription has been detected in human tumor cells or normal ones, while HERV LTR elements have shown the bidirectional promoter activity (Medstrand et al., 2001; Nigumann et al., 2002; Dunn et al., 2003; Sin et al., 2006). Those elements could provide biological role of organismal complexity by transcriptional diversity (Landry et al., 2003). Here, we developed a database for understanding the mechanism of cancer develop- ment in relation to TEs in human ESTsequences, and conducted experiemental validation using RT-PCR in tumor/adjacent normal tissues and corresponding cancer cell linesto confirm the candidate marker transcripts. Hypothetical model for retroelements in human genome Table. Potential splice site are utilized by transposable elements fusion exons Transposable elements Type of potential splicing site SINE Family LINE Family LTR Family DNA Family Accept&Donor 83 68 50 12 Accept Site 271 110 33 28 Materials & Methods Donor Site 216 80 43 18 TJP2 tight junction protein 2 (zona occludens 2) Chr.9 1 23 NM_004817.2 RT-PCR & Real-time PCR 168 bp 1 21 NM_201629.1 GAPDH 120 bp tumor/adjacent normal tissues q21.11 AW604158 colon(N) colon(C) Coding region Untranslated region Bioinformatics AluJo/FRAM colon(N) colon(C) NCBI,BLAST,MEGA3 AKR1C2 aldo-keto reductase family 1, member C2 liver(C) Chr.10 liver(N) liver(N) liver(N) liver(C) liver(C) 1 10 p15.1 DATABASE NM_2058453.1 1 11 300 bp NM_001354.4 GAPDH 120 bp CB106780 30 cycle 32cycle 34 cycle LTR/MaLR MLT1L LTR/MaLR MSTA LINE/L1 References • Kim TH, Jeon YJ, Kim WY, Kim HS: HESAS: HERVs expression and structure analysis system. Bioinformatics 2005, 15:1699-1970. • 2. Kim DS, Kim TH, Huh JW, Kim IC, Kim SW, Park HS, Kim HS : LINE FUSION GENES: a database of LINE expression in human genes. BMC Genomic 2006, 7:139 Genome Information Lab