3'UTR在基因表达调控中的作用

doi:10.16431/j.cnki.1671-7236.2016.11.015

摘要/Abstract

摘要：

真核生物的基因表达调控在生物体生长发育过程中发挥着重要作用，涉及转录、翻译及mRNA和蛋白质的周转等多种生物学过程。研究表明，mRNA的3'端非翻译区（3'UTR）与转录后基因表达关系密切，3'UTR在mRNA稳定性、亚细胞定位及翻译等生物学过程中发挥着重要的调控作用。3'UTR序列的变异，可引起基因的异常表达，导致疾病发生。作者主要对3'UTR在基因表达调控、人类疫病和畜禽生产中的作用等研究进行了综述，以期为3'UTR调控机制在人类疫病诊断与治疗，以及畜禽生产中的应用提供理论依据。

关键词: 3'端非翻译区; mRNA; 基因表达调控

Abstract:

In eukaryotes,the regulation of gene expression plays an important role in the growth and development of organisms which is a multistep process that involves the transcription,translation and turnover of messenger RNAs（mRNA）and proteins.Researches have showed that the 3'untranslated region（3'UTR）of mRNA is emerging as critically important in regulating gene expression at post transcriptional levels.mRNA stability,localization and translation are largely determined by sequences in the 3'UTR.The aberrant regulation of 3'UTR will result in aberrant levels of expressed protein, enhancing metabolic changes and leading to disease.The researches of 3'UTR in the regulation of gene expression,human diseases and animal production were summarized and discussed in this paper to provide the reference for applications of 3'UTR in human disease diagnosis and treatment and animal performance.

Key words: 3'UTR; mRNA; gene expression regulation

中图分类号:

Q786

喻世刚, 王钢. 3'UTR在基因表达调控中的作用[J]. 《中国畜牧兽医》, 2016, 43(11): 2907-2913.

YU Shi-gang, WANG Gang. Role of 3' Untranslated Region（3'UTR）in the Regulation of Gene Expression[J]. , 2016, 43(11): 2907-2913.

参考文献

[1] Komili S,Silver P A.Coupling and coordination in gene expression processes:A systems biology view[J].Nature Reviews Genetics,2008,9(1):38-48.
[2] Schwanhäusser B,Busse D,Li N,et al.Global quantification of mammalian gene expression control[J].Nature,2011,73(7347):337-342.
[3] Vogel C,Abreu Rde S,Ko D,et al.Sequence signatures and mRNA concentration can explain two-thirds of protein abundance variation in a human cell line[J].Molecular Systems Biology,2010,6(1):400-408.
[4] Quattrone A,Dassi E.Introduction to bioinformatics resources for post-transcriptional regulation of gene expression[J].Methods Mol Biol,2016,1358:3-28.
[5] Iacono M,Mignone F,Pesole G.uAUG and uORFs in human and rodent 5'untranslated mRNAs[J].Gene,2005,349:97-105.
[6] Tsuzaka K,Itami Y,Kumazawa C,et al.Conservative sequences in 3'UTR of TCRzeta mRNA regulate TCRzeta in SLE T cells[J].Biochemical&Biophysical Research Communications,2008,367(2):311-317.
[7] Mayr C.Evolution and biological roles of alternative 3'UTRs[J].Trends in Cell Biology,2015,26(3):227-237.
[8] Zlotorynski E.RNA:3'UTR alternatives to protein localization[J].Nature Reviews Molecular Cell Biology,2015,16(6):327-327.
[9] Mignone F,Gissi C,Liuni S,et al.Untranslated regions of mRNAs[J].Genome Biol,2002,3(3):1-10.
[10] Hou J,An X,Song Y,et al.Two mutations in the caprine MTHFR 3'UTR regulated by microRNAs are associated with milk production traits[J].PLoS One,2015,10(7):e0133015.
[11] De Jong V,Zaldumbide A,van der Slik A,et al.Variation in the CTLA43'UTR has phenotypic consequences for autoreactive T cells and associates with genetic risk for type 1 diabetes[J].Genes and Immunity,2016,17(1):75-78.
[12] Chatterjee S,Pal J K.Role of 5'-and 3'-untranslated regions of mRNAs in human diseases[J].Biology of the Cell,2009,101(5):251-262.
[13] Moore M J.From birth to death:The complex lives of eukaryotic mRNAs[J].Science,2005,309(5740):1514-1518.
[14] Carthew R W,Sontheimer E J.Origins and mechanisms of miRNAs and siRNAs[J].Cell,2009,136(4):642-655.
[15] Sin C,Chiarugi D,Valleriani A.Single-molecule modeling of mRNA degradation by miRNA:Lessons from data[J].BMC Syst Biol,2015,9(3):1752-0509.
[16] Küspert M,Murakawa Y,Schäffler K,et al.LARP4B is an AU-rich sequence associated factor that promotes mRNA accumulation and translation[J].RNA,2015,21(7):1294-1305.
[17] Barreau C,Paillard L,Osborne H B.AU-rich elements and associated factors:Are there unifying principles?[J].Nucleic Acids Research,2005,33(22):7138-7150.
[18] Vlasova I A,Tahoe N M,Fan D,et al.Conserved GU-rich elements mediate mRNA decay by binding to CUG-binding protein 1[J].Molecular Cell,2008,29(2):263-270.
[19] Vlasova-St L I,Bohjanen P R.Coordinate regulation of mRNA decay networks by GU-rich elements and CELF1[J].Current Opinion in Genetics&Development,2011,21(4):444-451.
[20] Kovarik P,Ebner F,Sedlyarov V.Posttranscriptional regulation of cytokine expression[J].Cytokine,2015,Ahead of publish.
[21] Djuranovic S,Nahvi A,Green R.miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay[J].Science,2012,336(6078):237-240.
[22] Li Y,Wang X,Yu J,et al.miR-122 targets the vanin 1 gene to regulate its expression in chickens[J].Poult Sci,2016,95(5):1145-1150.
[23] Zhang Y,Sturgis E M,Sun Y,et al.A functional variant at miRNA-122 binding site in IL-1α 3' UTR predicts risk and HPV-positive tumours of oropharyngeal cancer[J].European Journal of Cancer,2015,51(11):1415-1423.
[24] Andreassi C,Riccio A.To localize or not to localize:mRNA fate is in 3'UTR ends[J].Trends in Cell Biology,2009,19(9):465-474.
[25] Merianda T T,Gomes C,Yoo S,et al.Axonal localization of neuritin/CPG15 mRNA in neuronal populations through distinct 5' and 3'UTR elements[J].J Neurosci,2013,33(34):13735-13742.
[26] Lécuyer E,Yoshida H,Parthasarathy N,et al.Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function[J].Cell,2007,131(1):174-187.
[27] Mardakheh F K,Paul A,Kümper S,et al.Global analysis of mRNA,translation,and protein localization:Local translation is a key regulator of cell protrusions[J].Developmental Cell,2015,35(3):344-357.
[28] Jambor H,Surendranath V,Kalinka A T,et al.Systematic imaging reveals features of localized mRNAs and their changing subcellular destinations in development[J].Biorxiv,2014,4:008938.
[29] Jambor H,Surendranath V,Kalinka A T,et al.Systematic imaging reveals features and changing localization of mRNAs in Drosophila development[J].Elife,2015,4:e05003.
[30] Berkovits B D,Mayr C.Alternative 3'UTRs act as scaffolds to regulate membrane protein localization[J].Nature,2015,522(7556):363-367.
[31] Dever T E.Gene-specific regulation by general translation factors[J].Cell,2002,108(4):545-556.
[32] Mercer T R,Wilhelm D,Dinger M E,et al.Expression of distinct RNAs from 3'untranslated regions[J].Nucleic Acids Research,2011,39(6):2393-2403.
[33] Jenny A,Hachet O,Závorszky P,et al.A translation-independent role of oskar RNA in early Drosophila oogenesis[J].Development,2006,133(15):2827-2833.
[34] Jupe E R,Liu X T,Kiehlbauch J L,et al.The 3'untranslated region of prohibitin and cellular immortalization[J].Experimental Cell Research,1996,224(1):128-135.
[35] Amack J D,Paguio A P,Mahadevan M S.Cis and trans effects of the myotonic dystrophy（DM）mutation in a cell culture model[J].Human Molecular Genetics,1999,8(11):1975-1984.
[36] Zhang H,Ju Y L,Tian B.Biased alternative polyadenylation in human tissues[J].Genome Biology,2005,6(12):R100.
[37] Minguzzi S,Selcuklu S D,Spillane C,et al.An NTD-associated polymorphism in the 3'UTR of MTHFD1L can affect disease risk by altering miRNA binding[J].Hum Mutat,2014,35(1):96-104.
[38] Sandberg R,Neilson J R,Sarma A,et al.Proliferating cells express mRNAs with shortened 3'untranslated regions and fewer microRNA target sites[J].Science,2008,320(5883):1643-1647.
[39] López D S I,Quesada M P,Esteller M.Aberrant regulation of messenger RNA 3'-untranslated region in human cancer[J].Cell Oncol,2007,29(1):1-17.
[40] Wang W,Yuan P,Yu D,et al.A single-nucleotide polymorphism in the 3'-UTR region of the adipocyte fatty acid binding protein 4 gene is associated with prognosis of triple-negative breast cancer[J].Oncotarget,2016,4(10):7920.
[41] Romeo C,Weber M C,Zarei M,et al.HuR contributes to TRAIL resistance by restricting death receptor 4 expression in pancreatic cancer cells[J].Molecular Cancer Research,2016,14(7):599-611.
[42] Blaxall B C,Dwyer-Nield L D,Bauer A K,et al.Differential expression and localization of the mRNA binding proteins,AU-rich element mRNA binding protein（AUF1）and Hu antigen R（HuR),in neoplastic lung tissue[J].Molecular Carcinogenesis,2000,28(2):76-83.
[43] Prior J F,Lim E,Lingam N,et al.A moderately severe alpha-thalassemia condition resulting from a combination of the alpha2 polyadenylation signal(AATAAA——>AATA--）mutation and a 3.7 kb alpha gene deletion in an Australian family[J].Hemoglobin,2007,31(2):173-177.
[44] Jebbawi F,Fayyad-Kazan H,Merimi M,et al.A microRNA profile of human CD8⁺ regulatory T cells and characterization of the effects of microRNAs on Treg cell-associated genes[J].Journal of Translational Medicine,2014,12(1):1-16.
[45] Wang Y,Wu X S,He J,et al.A novel TP53 variant（rs78378222 A>C）in the polyadenylation signal is associated with increased cancer susceptibility:Evidence from a meta-analysis[J].Oncotarget,2016,27(10):1-12.
[46] Ceolin L,Romitti M,Rodrigues S D,et al.Effect of 3'UTR RET variants on RET mRNA secondary structure and disease presentation in medullary thyroid carcinoma[J].PLoS One,2016,11(2):e0147840.
[47] Reamon-Buettner S M,Cho S H,Borlak J.Mutations in the 3'-untranslated region of GATA4 as molecular hotspots for congenital heart disease(CHD)[J].BMC Medical Genetics,2007,8(1):38-49.
[48] Sui W,Zheng C,Ming Y,et al.Study on 3'-UTR length polymorphism in peripheral blood mononuclear cells of uremia patient[J].Renal Failure,2016,38(1):36-39.
[49] Zang L,Wang Y,Sun B,et al.Identification of a 13bp indel polymorphism in the 3'-UTR of DGAT2 gene associated with backfat thickness and lean percentage in pigs[J].Gene,2016,576(2):729-733.
[50] Li L,Huang J,Zhang X,et al.One SNP in the 3'-UTR of HMGB1 gene affects the binding of target bta-miR-223 and is involved in mastitis in dairy cattle[J].Immunogenetics,2012,64(11):817-824.
[51] Rong E,Zhang Z,Qiao S,et al.Functional characterization of a single nucleotide polymorphism in the 3'untranslated region of sheep DLX3 gene[J].PLoS One,2015,10(9):e0137135.
[52] Cui H,Yang S,Wang H,et al.The effect of a mutation in the 3-UTR region of the HMGCR gene on cholesterol in Beijing-you chickens[J].Animal Biotechnology,2010,21(4):241-251.
[53] 张抒,张强,张萌,等.miRNA对乳腺发育及泌乳调节作用的研究进展[J].中国畜牧兽医,2015,42(3):663-667.
[54] Bruhn O,Drerup K,Kaehler M,et al.Length variants of the ABCB13'-UTR and loss of miRNA binding sites:Possible consequences in regulation and pharmacotherapy resistance[J].Pharmacogenomics,2016,17(4):327-340.
[55] 贾小云,金雷皓,苗潋涓,等.miR-663通过靶向TGF-β1调控羊驼黑色素细胞的黑色素生成[J].中国农业科学,2015,48(1):165-173.
[56] Zhang W,Wei W,Yuanyuan Z,et al.The microRNA,miR-29c,participates in muscle development through targeting the YY1 gene and is associated with postmortem muscle pH in pigs[J].Frontiers of Agricultural Science and Engineering,2016,2(4):311-317.
[57] Horikawa A,Ogasawara H,Okada K,et al.Grazing-induced changes in muscle microRNA-206 and-208b expression in association with myogenic gene expression in cattle[J].Animal Science Journal,2015,86(11):952-960.