反式剪接及其在哺乳动物中的作用

doi:10.11843/j.issn.0366-6964.2018.10.002

摘要/Abstract

摘要：

反式剪接（trans-splicing，TS）是指两个或两个以上pre-mRNA分子经过剪接形成一个成熟mRNA的过程，是一种在转录后水平产生嵌合RNAs的方式。TS研究起步较晚，但高通量测序和生物信息学技术的发展，为相关研究提供了有效手段。伴随着大量TS及其嵌合RNAs被鉴定，人们发现TS可以产生新的功能性产物——融合蛋白或调控性非编码RNA，也可以仅仅通过竞争性使用亲本基因的pre-mRNA而影响亲本基因表达，从而在生理活动、疾病发生中发挥作用。本文就TS定义、类型、产生机制及其在哺乳动物中的作用等方面进行综述，以期为人们全面了解TS的研究概况及发展趋势提供参考。

Abstract:

Trans-splicing(TS) is the process by which two or more pre-mRNA molecules are spliced to form a mature mRNA, a way to produce chimeric RNAs at the post-transcriptional level. TS research started late, but the development of high-throughput sequencing and bioinformatics technologies has provided the effective means for related research. Along with the identification of a large number of TS and its chimeric RNAs, it has been found that TS can produce new functional products-fusion proteins or regulatory non-coding RNAs, also can affect parental genes expression only by competitive use of the parental pre-mRNA, which play important role in physiological activities and diseases. This article reviews the TS definition, type, production mechanism and its role in mammals, in order to provide a reference for completely understanding the research situation and development trend of TS.

中图分类号:

Q956

荆晓燕, 张彩霞, 宋艳芳, 刘东宇, 刘娣, 杨秀芹. 反式剪接及其在哺乳动物中的作用[J]. 畜牧兽医学报, 2018, 49(10): 2070-2079.

JING Xiao-yan, ZHANG Cai-xia, SONG Yan-fang, LIU Dong-yu, LIU Di, YANG Xiu-qin. Trans-splicing and Its Roles in Mammals[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2018, 49(10): 2070-2079.

0
/ / 推荐

导出引用管理器 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

链接本文: https://www.xmsyxb.com/CN/10.11843/j.issn.0366-6964.2018.10.002

https://www.xmsyxb.com/CN/Y2018/V49/I10/2070

参考文献

[1] LEI Q,LI C,ZUO Z X,et al.Evolutionary insights into RNA trans-splicing in vertebrates[J].Genome Biol Evol,2016,8(3):562-577.
[2] KRCHÑÁKOVÁ Z,KRAJOVI J,VESTEG M.On the possibility of an early evolutionary origin for the spliced leader trans-splicing[J].J Mol Evol,2017,85(1-2):37-45.
[3] PREUÉER C,JAÉ N,GVNZL A,et al.Pre-mRNA splicing in Trypanosoma brucei:Factors,mechanisms,and regulation[C]//BINDEREIF A.RNA Metabolism in Trypanosomes.Berlin,Heidelberg:Springer,2012:49-77.
[4] ALLEN M A,HILLIER L W,WATERSTON R H,et al.A global analysis of C.elegans trans-splicing[J].Genome Res,2011,21(2):255-264.
[5] MCMANUS C J,DUFF M O,EIPPER-MAINS J,et al.Global analysis of trans-splicing in Drosophila[J].Proc Natl Acad Sci U S A,2010,107(29):12975-12979.
[6] SHAO W,ZHAO Q Y,WANG X Y,et al.Alternative splicing and trans-splicing events revealed by analysis of the Bombyx mori transcriptome[J].RNA,2012,18(7):1395-1407.
[7] CAUDEVILLA C,SERRA D,MILIAR A,et al.Natural trans-splicing in carnitine octanoyltransferase pre-mRNAs in rat liver[J].Proc Natl Acad Sci U S A,1998,95(21):12185-12190.
[8] DI TOMMASO S,ANTONACCI R,CICCARESE S,et al.Extensive analysis of D-J-C arrangements allows the identification of different mechanisms enhancing the diversity in sheep T cell receptor β-chain repertoire[J].BMC Genomics,2010,11:3.
[9] SULLIVAN P M,PETRUSZ P,SZPIRER C,et al.Alternative processing of androgen-binding protein RNA transcripts in fetal rat liver:identification of a transcript formed by trans splicing[J].J Biol Chem,1991,266(1):143-154.
[10] MA E S K,WAN T S K,AU C H,et al.Next-generation sequencing and molecular cytogenetic characterization of ETV6-LYN fusion due to chromosomes 1,8 and 12 rearrangement in acute myeloid leukemia[J].Cancer Genet,2017,218-219:15-19.
[11] MITTAL V K,MCDONALD J F.De novo assembly and characterization of breast cancer transcriptomes identifies large numbers of novel fusion-gene transcripts of potential functional significance[J].BMC Med Genomics,2017,10:53.
[12] BABICEANU M,QIN F J,XIE Z Q,et al.Recurrent chimeric fusion RNAs in non-cancer tissues and cells[J].Nucleic Acids Res,2016,44(6):2859-2872.
[13] FANG W W,WEI Y,KANG Y B,et al.Detection of a common chimeric transcript between human chromosomes 7 and 16[J].Biol Direct,2012,7:49.
[14] GREWE F,VIEHOEVER P,WEISSHAAR B,et al.A trans-splicing group I intron and tRNA-hyperediting in the mitochondrial genome of the lycophyte Isoetes engelmannii[J].Nucleic Acids Res,2009,37(15):5093-5104.
[15] GLANZ S,KVCK U.Trans-splicing of organelle introns-a detour to continuous RNAs[J].Bioessays,2009,31(9):921-934.
[16] RANDAU L,MVNCH R,HOHN M J,et al.Nanoarchaeum equitans creates functional tRNAs from separate genes for their 5'-and 3'-halves[J].Nature,2005,433(7025):537-541.
[17] MA L,YANG S L,ZHAO W M,et al.Identification and analysis of pig chimeric mRNAs using RNA sequencing data[J].BMC Genomics,2012,13:429.
[18] HANNON G J,MARONEY P A,NILSEN T W.U small nuclear ribonucleoprotein requirements for nematode cis-and trans-splicing in vitro[J].J Biol Chem,1991,266(34):22792-22795.
[19] PREUΒER C,ROSSBACH O,HUNG L H,et al.Genome-wide RNA-binding analysis of the trypanosome U1 snRNP proteins U1C and U1-70K reveals cis/trans-spliceosomal network[J].Nucleic Acids Res,2014,42(10):6603-6615.
[20] STERN M Z,GUPTA S K,SALMON-DIVON M,et al.Multiple roles for polypyrimidine tract binding (PTB) proteins in trypanosome RNA metabolism[J].RNA,2009,15(4):648-665.
[21] DE GAUDENZI J G,JÄGER A V,IZCOVICH R,et al.Insights into the regulation of mRNA processing of polycistronic transcripts mediated by DRBD4/PTB2,a trypanosome homolog of the polypyrimidine tract-binding protein[J].J Eukaryot Microbiol,2016,63(4):440-452.
[22] PHILIPPE L,PANDARAKALAM G C,FASIMOYE R,et al.An in vivo genetic screen for genes involved in spliced leader trans-splicing indicates a crucial role for continuous de novo spliced leader RNP assembly[J].Nucleic Acids Res,2017,45(14):8474-8483.
[23] GUPTA S K,KOSTI I,PLAUT G,et al.The hnRNP F/H homologue of Trypanosoma brucei is differentially expressed in the two life cycle stages of the parasite and regulates splicing and mRNA stability[J].Nucleic Acids Res,2013,41(13):6577-6594.
[24] MURPHY W J,WATKINS K P,AGABIAN N.Identification of a novel Y branch structure as an intermediate in trypanosome mRNA processing:Evidence for trans splicing[J].Cell,1986,47(4):517-525.
[25] MICHAELI S.Trans-splicing in trypanosomes:Machinery and its impact on the parasite transcriptome[J].Future Microbiol,2011,6(4):459-474.
[26] DIXON R J,EPERON I C,SAMANI N J.Complementary intron sequence motifs associated with human exon repetition:A role for intragenic,inter-transcript interactions in gene expression[J].Bioinformatics,2007,23(2):150-155.
[27] KAMIKAWA R,INAGAKI Y,TOKORO M,et al.Split introns in the genome of Giardia intestinalis are excised by spliceosome-mediated trans-splicing[J].Curr Biol,2011,21(4):311-315.
[28] FISCHER S E J,BUTLER M D,PAN Q,et al.Trans-splicing in C.elegans generates the negative RNAi regulator ERI-6/7[J].Nature,2008,455(7212):491-496.
[29] YANG Y F,ZHANG X Q,MA X H,et al.Trans-splicing enhances translational efficiency in C.elegans[J].Genome Res,2017,27(9):1525-1535.
[30] LI B L,LI X L,DUAN Z J,et al.Human acyl-CoA:Cholesterol acyltransferase-1(ACAT-1) gene organization and evidence that the 4.3-kilobase ACAT-1 mRNA is produced from two different chromosomes[J].J Biol Chem,1999,274(16):11060-11071.
[31] YANG L,LEE O,CHEN J,et al.Human acyl-coenzyme A:Cholesterol acyltransferase 1(acat1) sequences located in two different chromosomes (7 and 1) are required to produce a novel ACAT1 isoenzyme with additional sequence at the N terminus[J].J Biol Chem,2004,279(44):46253-46262.
[32] ZHANG L,LU H,XIN D Z,et al.A novel ncRNA gene from mouse chromosome 5 trans-splices with Dmrt1 on chromosome 19[J].Biochem Biophys Res Commun,2010,400(4):696-700.
[33] NI M J,HU Z H,LIU Q,et al.Identification and characterization of a novel non-coding RNA involved in sperm maturation[J].PLoS One,2011,6(10):e26053.
[34] HIRANO M,NODA T.Genomic organization of the mouse Msh4 gene producing bicistronic,chimeric and antisense mRNA[J].Gene,2004,342(1):165-177.
[35] GUERRA E,TREROTOLA M,DELL' ARCIPRETE R,et al.A bicistronic CYCLIN D1-TROP2 mRNA chimera demonstrates a novel oncogenic mechanism in human cancer[J].Cancer Res,2008,68(19):8113-8121.
[36] PLEBANI R,OLIVER G R,TREROTOLA M,et al.Long-range transcriptome sequencing reveals cancer cell growth regulatory chimeric mRNA[J].Neoplasia,2012,14(11):1087-1096.
[37] HANAHAN D,WEINBERG R A.Hallmarks of cancer:The next generation[J].Cell,2011,144(5):646-674.
[38] ZHOU J H,LIAO J,ZHENG X X,et al.Chimeric RNAs as potential biomarkers for tumor diagnosis[J].BMB Rep,2012,45(3):133-140.
[39] KANNAN K,WANG L G,WANG J H,et al.Recurrent chimeric RNAs enriched in human prostate cancer identified by deep sequencing[J].Proc Natl Acad Sci U S A,2011,108(22):9172-9177.
[40] DANG J,NANCE S,MA J,et al.AMKL chimeric transcription factors are potent inducers of leukemia[J].Leukemia,2017,31(10):2228-2234.
[41] XIE Z Q,BABICEANU M,KUMAR S,et al.Fusion transcriptome profiling provides insights into alveolar rhabdomyosarcoma[J].Proc Natl Acad Sci U S A,2016,113(46):13126-13131.
[42] LEE J R,KWON C H,CHOI Y,et al.Transcriptome analysis of paired primary colorectal carcinoma and liver metastases reveals fusion transcripts and similar gene expression profiles in primary carcinoma and liver metastases[J].BMC Cancer,2016,16:539.
[43] ENDO A,TOMIZAWA D,AOKI Y,et al.EWSR1/ELF5 induces acute myeloid leukemia by inhibiting p53/p21 pathway[J].Cancer Sci,2016,107(12):1745-1754.
[44] KOONTZ J I,LEE SORENG A,NUCCI M,et al.Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors[J].Proc Natl Acad Sci U S A,2001,98(11):6348-6353.
[45] LI H,WANG J L,MOR G,et al.A neoplastic gene fusion mimics trans-splicing of RNAs in normal human cells[J]. Science,2008,321(5894):1357-1361.
[46] OSBORNE C S,CHAKALOVA L,MITCHELL J A,et al.Myc dynamically and preferentially relocates to a transcription factory occupied by Igh[J].PLoS Biol,2007,5(8):e192.
[47] SORENSEN P H B,LYNCH J C,QUALMAN S J,et al.PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma:A report from the children's oncology group[J].J Clin Oncol,2002,20(11):2672-2679.
[48] GRAF FINCKENSTEIN F,SHAHBAZIAN V,DAVICIONI E,et al.PAX-FKHR function as pangenes by simultaneously inducing and inhibiting myogenesis[J].Oncogene,2008,27(14):2004-2014.
[49] YUAN H L,QIN F J,MOVASSAGH M,et al.A chimeric RNA characteristic of rhabdomyosarcoma in normal myogenesis process[J].Cancer Discov,2013,3(12):1394-1403.
[50] ZAPHIROPOULOS P G.Trans-splicing in higher eukaryotes:Implications for cancer development?[J].Front Genet,2011,2:92.
[51] WU C S,YU C Y,CHUANG C Y,et al.Integrative transcriptome sequencing identifies trans-splicing events with important roles in human embryonic stem cell pluripotency[J].Genome Res, 2014, 24(1):25-36.
[52] CHATTERJEE T K,FISHER R A.Novel alternative splicing and nuclear localization of human RGS12 gene products[J].J Biol Chem, 2000, 275(38):29660-29671.
[53] FRENKEL-MORGENSTERN M,LACROIX V,EZKURDIA I,et al.Chimeras taking shape:Potential functions of proteins encoded by chimeric RNA transcripts[J].Genome Res, 2012, 22(7):1231-1242.
[54] FRENKEL-MORGENSTERN M,VALENCIA A.Novel domain combinations in proteins encoded by chimeric transcripts[J].Bioinformatics, 2012, 28(12):i67-i74.
[55] HUANG R,KUMAR S,LI H.Absence of correlation between chimeric RNA and aging[J].Genes (Basel), 2017, 8(12):E386.
[56] BERGER A,MAIRE S,GAILLARD M C,et al.mRNA trans-splicing in gene therapy for genetic diseases[J].Wiley Interdiscip Rev RNA, 2016, 7(4):487-498.
[57] CRAWFORD T O, PARDO C A. The neurobiology of childhood spinal muscular atrophy[J].Neurobiol Dis,1996, 3(2):97-110.
[58] OSKOUI M, LEVY G, GARLAND C J, et al. The changing natural history of spinal muscular atrophy type I[J].Neurology, 2007, 69(20):1931-1936.
[59] LEFEBVRE S, BVRGLEN L, REBOULLET S, et al. Identification and characterization of a spinal muscular atrophy-determining gene[J].Cell,1995, 80(1):155-165.
[60] SUMNER C J.Therapeutics development for spinal muscular atrophy[J].NeuroRx, 2006, 3(2):235-245.
[61] COADY T H, LORSON C L. Trans-splicing-mediated improvement in a severe mouse model of spinal muscular atrophy[J].J Neurosci, 2010, 30(1):126-130.
[62] RINDT H, TOM C M, LORSON C L, et al. Optimization of trans-splicing for huntington's disease RNA therapy[J].Front Neurosci, 2017, 11:544.
[63] PEKING P,KOLLER U,DUARTE B,et al.An RNA-targeted therapy for dystrophic epidermolysis bullosa[J].Nucleic Acids Res, 2017, 45(17):10259-10269.
[64] PRONDZYNSKI M, KRÄMER E, LAUFER S D, et al.Evaluation of MYBPC3 trans-splicing and gene replacement as therapeutic options in human iPSC-derived cardiomyocytes[J].Mol Ther Nucleic Acids, 2017, 7:475-486.
[65] UCHIDA N, WASHINGTON K N, MOZER B,et al. RNA Trans-splicing targeting endogenous β-globin pre-messenger RNA in human erythroid cells[J].Hum Gene Ther Methods, 2017, 28(2):91-99.
[66] UCKUN F M,QAZI S,MA H,et al.CD22△E12 as a molecular target for corrective repair using RNA trans-splicing:Anti-leukemic activity of a rationally designed RNA trans-splicing molecule[J].Integr Biol (Camb),2015,7(2):237-249.
[67] HE X X,LIAO J Z,LIU F,et al.Functional repair of p53 mutation in colorectal cancer cells using trans-splicing[J]. Oncotarget,2015,6(4):2034-2045.
[68] AZIBANI F,BRULL A,ARANDEL L,et al.Gene therapy via trans-splicing for LMNA-related congenital muscular dystrophy[J].Mol Ther Nucleic Acids,2018,10:376-386.
[69] INGEMARSDOTTER C K,PODDAR S,MERCIER S,et al.Expression of herpes simplex virus thymidine kinase/ganciclovir by RNA Trans-splicing induces selective killing of HIV-producing cells[J].Mol Ther Nucleic Acids,2017,7:140-154.