综述

哺乳动物嵌合RNAs产生机制:cis-SAGe

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  • 东北农业大学动物科技学院,150030 哈尔滨
作者简介: 禚建树,硕士研究生,专业方向:分子遗传学与动物育种。E-mail: 452273653@qq.com|通讯作者: 杨秀芹,博士,博士生导师,研究方向:分子遗传学与动物育种。E-mail: xiuqin163@163.com

收稿日期: 2017-05-31

  修回日期: 2017-07-31

  网络出版日期: 2018-02-01

基金资助

黑龙江省科研机构创新能力提升专项(YC2016D001);黑龙江省留学归国科学基金项目资助(LC201412)

Generation of Chimeric RNAs by cis-splicing of adjacent genes (cis-SAGe) in mammals

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  • College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China

Received date: 2017-05-31

  Revised date: 2017-07-31

  Online published: 2018-02-01

Supported by

the Foundation for Improving Innovation Ability of Scientific Research Institution of Heilongjiang Province(YC2016D001);Scientific Research Foundation for the Returned Overseas Chinese Scholars of Heilongjiang Province(LC201412)

摘要

嵌合RNAs是指由两个或两个以上独立基因(即亲本基因)融合产生的新RNAs。传统观点认为,嵌合RNAs都是染色体重排的结果。近年来研究发现,相邻基因间的顺式剪接(cis-splicing of adjacent genes, cis-SAGe)也是产生嵌合RNAs的重要机制之一。cis-SAGe是同一条染色体上位置相邻、转录方向相同的基因间发生转录通读,由此产生的初始转录本经过加工,形成了含有两个或多个亲本基因序列的嵌合RNAs。cis-SAGe最初是在肿瘤细胞中被鉴定出来,其在肿瘤发生中的潜在功能引起了研究者的广泛兴趣。随着研究的深入,人们发现cis-SAGe也广泛存在于正常组织中,可能是哺乳动物进化过程中产生新基因的一种重要机制。本文就cis-SAGe的剪接和表达特性、产生机制及其产物的功能等方面进行了综述,以期为人们全面了解cis-SAGe的研究概况及发展趋势提供参考。

本文引用格式

禚建树, 荆晓燕, 杜欣, 杨秀芹 . 哺乳动物嵌合RNAs产生机制:cis-SAGe[J]. 遗传, 2018 , 40(2) : 145 -154 . DOI: 10.16288/j.yczz.17-197

Abstract

Chimeric RNA molecules, possessing exons from two or more independent genes, are traditionally believed to be produced by chromosome rearrangement. However, recent studies revealed that cis-splicing of adjacent genes (cis- SAGe) is one of the major mechanisms underlying the formation of chimeric RNAs. cis-SAGe refers to intergenic splicing of directly adjacent genes with the same transcriptional orientation, resulting in read-through transcripts, termed chimeric RNAs, which contain sequences from two or more parental genes. cis-SAGe was first identified in tumor cells, since then its potential in carcinogenesis has attracted extensive attention. More and more scientists are focusing on it. With the development of research, cis-SAGe was found to be ubiquitous in various normal tissues, and might make a crucial contribution to the formation of novel genes in the evolution of genomes. In this review, we summarize the splicing pattern, expression characteristics, possible mechanisms, and significance of cis-SAGe in mammals. This review will be helpful for general understanding of the current status and development tendency of cis-SAGe.

参考文献

[1] Ge HY , Liu KJ , Juan T , Fang F , Newman M , Hoeck W . FusionMap: detecting fusion genes from next-generation sequencing data at base-pair resolution. Bioinformatics, 2011, 27( 14): 1922- 1928.
[2] Gerstein MB , Bruce C , Rozowsky JS , Zheng DY , Du J , Korbel JO , Emanuelsson O , Zhang ZD , Weissman S , Snyder M . What is a gene, post-ENCODE? History and updated definition. Genome Res, 2007, 17( 6): 669- 681.
[3] Gingeras TR . Implications of chimaeric non-co-linear transcripts. Nature, 2009, 461( 7261): 206- 211.
[4] Rowley JD . Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature, 1973, 243( 5405): 290- 293.
[5] Skapek SX , Anderson J , Barr FG , Bridge JA , Gastier- Foster JM , Parham DM , Rudzinski ER , Triche T , Hawkins DS . PAX-FOXO1 fusion status drives unfavorable outcome for children with rhabdomyosarcoma: a children's oncology group report. Pediatr Blood Cancer, 2013, 60( 9): 1411- 1417.
[6] Missiaglia E , Williamson D , Chisholm J , Wirapati P , Pierron G , Petel F , Concordet JP , Thway K , Oberlin O , Pritchard-Jones K , Delattre O , Delorenzi M , Shipley J . PAX3/FOXO1 fusion gene status is the key prognostic molecular marker in rhabdomyosarcoma and significantly improves current risk stratification. J Clin Oncol, 2012, 30( 14): 1670- 1677.
[7] Jothi M1, Mal M, Keller C, Mal AK. Small molecule inhibition of PAX3-FOXO1 through AKT activation suppresses malignant phenotypes of alveolar rhabdomyosarcoma. Mol Cancer Ther, 2013, 12( 12): 2663- 2674.
[8] Loupe JM , Miller PJ , Ruffin DR , Stark MW , Hollenbach AD . Inhibiting phosphorylation of the oncogenic PAX3- FOXO1 reduces alveolar rhabdomyosarcoma phenotypes identifying novel therapy options. Oncogenesis, 2015, 4( 3): e145.
[9] Williamson D , Missiaglia E , De Reyniès A , Pierron G , Thuille B , Palenzuela G , Thway K , Orbach D , Laé M , Fréneaux P , Pritchard-Jones K , Oberlin O , Shipley J , Delattre O . Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J Clin Oncol, 2010, 28( 13): 2151- 2158.
[10] Tognon C , Knezevich SR , Huntsman D , Roskelley CD , Melnyk N , Mathers JA , Becker L , Carneiro F , MacPherson N, Horsman D, Poremba C, Sorensen PHB. Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell, 2002, 2( 5): 367- 376.
[11] Persson M , Andrén Y , Mark J , Horlings HM , Persson F , Stenman G . Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci USA, 2009, 106( 44): 18740- 18744.
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