Identification of a novel circularized transcript of the AML1 gene
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
The AML1 gene is an essential transcription factor regulating the differentiation of hematopoietic stem cells into mature blood cells. Though at least 12 different alternatively spliced AML1 mRNAs are generated, three splice variants (AML1a,AML1b and AML1c) have been characterized. Here, using the reverse transcription-polymerase chain reaction with outwardfacing primers, we identified a novel non-polyadenylated transcript from the AML1 gene, with exons 5 and 6 scrambled. The novel transcript resisted RNase R digestion, indicating it is a circular RNA structure that may originate from products of mRNA alternative splicing. The expression of the novel transcript in different cells or cell lines of human and a number of other species matched those of the canonical transcripts. The discovery provides additional evidence that circular RNA could stably exist in vivo in human, and may also help to understand the mechanism of the regulation of the AML1 gene transcription.
Abstract
The AML1 gene is an essential transcription factor regulating the differentiation of hematopoietic stem cells into mature blood cells. Though at least 12 different alternatively spliced AML1 mRNAs are generated, three splice variants (AML1a,AML1b and AML1c) have been characterized. Here, using the reverse transcription-polymerase chain reaction with outwardfacing primers, we identified a novel non-polyadenylated transcript from the AML1 gene, with exons 5 and 6 scrambled. The novel transcript resisted RNase R digestion, indicating it is a circular RNA structure that may originate from products of mRNA alternative splicing. The expression of the novel transcript in different cells or cell lines of human and a number of other species matched those of the canonical transcripts. The discovery provides additional evidence that circular RNA could stably exist in vivo in human, and may also help to understand the mechanism of the regulation of the AML1 gene transcription.
참고문헌 (22)
- De Braekeleer, E., "RUNX1 translocations and fusion genes in malignant hemopathies", Future Oncology, 7, pp.77~91 (2011)
- Burd, C. E., "Expression of linear and novel circular forms of an INK4", ARF-Associated Non-Coding RNA correlates with atherosclerosis risk, 2010, pp.6, e1001233~
- Suzuki, H., "Characterization of RNase R-digested cellular RNA source that consists of lariat and circular RNAs from pre-mRNA splicing", Nucleic Acids Res, 34, pp.e63~ (2006)
- Miyoshi, H., "Alternative splicing and genomic structure of the AML1 gene involved in acute myeloid leukemia", Nucleic Acids Res, 23, pp.2762~2769 (1995)
- Nigro, J., "Scrambled exons", Cell, 64, pp.607~613 (1991)
- Cocquerelle, C., "Splicing with inverted order of exons occurs proximal to large introns", EMBO J, 11, pp.1095~1098 (1992)
- Cocquerelle, C., "splicing yields circular RNA molecules", FASEB J, 7, pp.155~160 (1993)
- Capel, B., "Circular transcripts of the testis- determining gene Sry in adult mouse testis", Cell, 73, pp.1019~1030 (1993)
- Zaphiropoulos, P. G., "Circular RNAs from transcripts of the rat cytochrome P450 2C24 gene: correlation with exon skipping", Proc. Natl. Acad. Sci, 93, pp.6536~6541 (1996)
- Zaphiropoulos, P. G., "Exon skipping and circular RNA formation in transcripts of the human cytochrome P-450 2C18 gene in epidermis and of the rat androgen binding protein gene in testis", Mol. Cell. Biol, 17, pp.2985~2993 (1997)
- Surono, A., "Circular dystrophin RNAs consisting of exons that were skipped by alternative splicing", Hum. Mol. Genet, 8, pp.493~500 (1999)
- Gualandi, F., "Multiple exon skipping and RNA circularisation contribute to the severe phenotypic expression of exon 5 dystrophin deletion", J. Med. Genet, 40, pp.e100~ (2003)
- Li, X. F., "A circularized sodium-calcium exchanger exon 2 transcript", J. Biol. Chem, 274, pp.8153~8160 (1999)
- Sänger, H. L., "Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures", Proc. Natl. Acad. Sci, 73, pp.3852~3856 (1976)
- Salzman, J., "Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types", PloS ONE, 7, pp.e30733~ (2012)
- Takahara, T., "Heterogeneous Sp1 mRNAs in human HepG2 cells include a product of homotypic trans-splicing", J. Biol. Chem, 275, pp.38067~38072 (2000)
- Flouriot, G., "Natural trans-spliced mRNAs are generated from the human estrogen receptor-α (hERα) gene", J. Biol. Chem, 8, pp.218~222 (2002)
- Axtell, M. J., "Vive la différence: biogenesis and evolution of microRNAs in plants and animals", Genome Biol, 12, pp.221~ (2011)
- Chen, C. Y., "Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs", Science, 268, pp.415~417 (1995)
- Kozak, M., "The scanning model for translation: an update", J. Cell Biol, 108, pp.229~241 (1989)
- Sachs, A. B., "The poly(A) binding protein is required for poly(A) shortening and 60s ribosomal subunit-dependent translation initiation", Cell, 58, pp.857~867 (1989)
- Storzm, G., "An expanding universe of noncoding RNAs", Science, 296, pp.1260~1263 (2002)