Identification and characterization of an imprinted antisense RNA (MESTIT1) in the human MEST locus on chromosome 7q32

被引:49
作者
Nakabayashi, K
Bentley, L
Hitchins, MP
Mitsuya, K
Meguro, M
Minagawa, S
Bamforth, JS
Stanier, P
Preece, M
Weksberg, R
Oshimura, M
Moore, GE
Scherer, SW
机构
[1] Hosp Sick Children, Dept Genet, Toronto, ON M5G 1X8, Canada
[2] Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada
[3] Univ London Imperial Coll Sci Technol & Med, Fac Med, Inst Reprod & Dev Biol, Dept Fetal & Maternal Med, London, England
[4] Tottori Univ, Fac Med, Dept Mol & Cell Genet, Tottori 680, Japan
[5] Yokohama City Univ, Grad Sch Integrated Sci, Kihara Inst Biol Res, Yokohama, Kanagawa 232, Japan
[6] Univ Alberta, Dept Med Genet, Edmonton, AB, Canada
基金
加拿大健康研究院; 英国惠康基金;
关键词
D O I
10.1093/hmg/11.15.1743
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Imprinted gene(s) on human chromosome 7 are thought to be involved in Russell-Silver syndrome (RSS), based on the fact that similar to10% of patients have maternal uniparental disomy of chromosome 7. However, involvement of the known imprinted genes (GRB10 at 7p12, PEG10 at 7q21.3 and MEST at 7q32) in RSS has yet to be established. To screen for new imprinted genes, we are initially using somatic cell hybrids containing a paternal or maternal human chromosome 7. Transcripts located between D7S530 and D7S649 (a 1.5 Mb interval encompassing MEST) were subjected to RT-PCR analysis using somatic cell hybrids. One transcript named MESTIT1 (for MEST intronic transcript 1) reproducibly showed paternal-specific expression. Upon further analysis, we found MESTIT1 to be (1) paternally (and not maternally) expressed in all fetal tissues and fibroblasts examined, (2) to be located in an intron of one of the two isoforms of MEST but transcribed in the opposite direction, (3) to be composed of at least two exons without any significant open reading frame, and (4) to exist as a 4.2 kb transcript in many fetal and adult tissues. We could also identify two isoforms of the mouse Mest gene as observed in humans, but it is still unknown if a murine ortholog of MESTIT1 exists. We also examined the imprinting status of MEST isoforms as a first step in assessing whether MESTIT1 might influence the allelic expression pattern of the sense transcript. MEST isoform 1 was determined to be exclusively expressed from the paternal allele in all fetal tissues and cell lines examined, whereas MEST isoform 2 was only preferentially expressed from the paternal allele in a tissue/cell-type-specific manner. Our results suggest that MESTIT1 is a paternally expressed non-coding RNA that may be involved in the regulation of MEST expression during development. MESTIT1 (also known as PEG1-AS) is now the third independent transcript (with MEST and COPG21T1) identified at human chromosome 7q32 demonstrating paternal chromosome-specific expression.
引用
收藏
页码:1743 / 1756
页数:14
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