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浙江大学学报(农业与生命科学版)  2021, Vol. 47 Issue (3): 295-302    DOI: 10.3785/j.issn.1008-9209.2020.07.152
综述     
昆虫N6-甲基腺嘌呤的研究进展
赵书荻1(),吴小锋1,2()
1.浙江大学动物科学学院蚕蜂研究所,杭州 310058
2.浙江省蚕蜂资源利用与创新研究重点实验室,杭州 310058
Research advance of N6-methyladenosine (m6A) in insect
Shudi ZHAO1(),Xiaofeng WU1,2()
1.Institute of Sericulture and Apiculture, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
2.Key Laboratory of Silkworm and Bee Resource Utilization and Innovation of Zhejiang Province, Hangzhou 310058, China
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摘要:

RNA修饰在真核生物的基因表达调控中具有重要意义,N 6-甲基腺嘌呤(N 6-methyladenosine, m6A)是RNA修饰中最常见的一种,可通过影响信使RNA(mRNA)的代谢过程来调控一系列生命活动。本文主要根据近年来在昆虫方面的相关研究成果,归纳了m6A调控酶和识别蛋白的作用机制和m6A动态调控的过程,分析了m6A在mRNA中的分布规律,总结了m6A在昆虫中的典型生物学功能。并从当前研究存在的空白与不足、有待进一步探索的科学问题等方面,对m6A未来在昆虫领域的研究前景进行了展望,以期为后续的研究与探索提供参考。

关键词: RNA修饰N 6-甲基腺嘌呤昆虫调控机制功能    
Abstract:

RNA modifications play vital roles in regulating gene expression of eukaryotes. The most prevalent RNA modification among them is N 6-methyladenosine (m6A), which is involved in a series of physiological activities. The mechanism of m6A regulatory enzymes as well as reader proteins, the process of m6A dynamic regulation, and the regular pattern of m6A distribution in mRNAs were introduced, and the typical biological functions of m6A mainly according to the recent progresses made in insects were summarized. Above the review, we preview the research and application prospects of m6A from the aspects of vacancies existing in current study and related phenomenon to be explain, aimed at forming the latest reference for exploration of m6A in insects.

Key words: RNA modification    N 6-methyladenosine (m6A)    insect    regulatory mechanism    function
收稿日期: 2020-07-15 出版日期: 2021-06-25
CLC:  Q 71  
基金资助: 国家自然科学基金(31772675);浙江省自然科学基金(LZ20C170001)
通讯作者: 吴小锋     E-mail: 2667140402@qq.com;wuxiaofeng@zju.edu.cn
作者简介: 赵书荻(https://orcid.org/0000-0001-5949-9465),E-mail:2667140402@qq.com
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引用本文:

赵书荻,吴小锋. 昆虫N6-甲基腺嘌呤的研究进展[J]. 浙江大学学报(农业与生命科学版), 2021, 47(3): 295-302.

Shudi ZHAO,Xiaofeng WU. Research advance of N6-methyladenosine (m6A) in insect. Journal of Zhejiang University (Agriculture and Life Sciences), 2021, 47(3): 295-302.

链接本文:

http://www.zjujournals.com/agr/CN/10.3785/j.issn.1008-9209.2020.07.152        http://www.zjujournals.com/agr/CN/Y2021/V47/I3/295

图1  m6A的动态调控与识别蛋白
图2  不同物种m6A相关蛋白同源物系统进化分析A. m6A甲基转移酶;B. YTHDC1;C. YTHDC2;D. YTHDF1;E. YTHDF2;F. YTHDF3。Dr:斑马鱼;Dm:黑腹果蝇;Hs:人;Mm:小鼠; Rn:大鼠;At:拟南芥;Xl:非洲爪蟾;Sc:酿酒酵母;Bm:家蚕。
图3  m6A修饰在mRNA中的位置分布

蛋白

Protein

物种

Species

功能

Function

Ime4果蝇

参与Sxl的剪接,调控果蝇的性别

分化[18,38-40]

调控神经系统发育,缺失后丧失飞

行和运动能力[40]

通过激活Notch通路参与卵细胞的

产生[5]

BmMETTL3家蚕

维持细胞周期和中期纺锤体正常

排列[19]

抑制杆状病毒VP39的表达[37]
METTL14果蝇调控果蝇神经系统的发育[40]

调控Sxl的可变剪接,控制果蝇的性

别分化[38-39]

BmMETTL14家蚕

维持细胞周期和中期纺锤体正常

排列[19]

抑制杆状病毒VP39的表达[37]
fl(2)d果蝇

参与Sxl的剪接,被敲除导致胚胎

死亡[41]

控制视网膜发育[42]
Nito果蝇

调控Wnt信号通路和感光器的

发育[43]

参与Sxl的可变剪接[44]
YTH521-B果蝇

参与Sxl的可变剪接和神经系统

的发育[40]

BmYTHDF3家蚕抑制杆状病毒VP39的表达[37]
表1  m6A相关蛋白的生物学功能
图4  Sxl介导性别分化的下游通路
图5  Sxl mRNA的可变剪接
1 NACHTERGAELE S, HE C. The emerging biology of RNA post-transcriptional modifications. RNA Biology, 2017,14(2):156-163. DOI:10.1080/15476286.2016.1267096
doi: 10.1080/15476286.2016.1267096
2 YANG Y, HSU P J, CHEN Y S, et al. Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism. Cell Research, 2018,28(6):616-624. DOI:10.1038/s41422-018-0040-8
doi: 10.1038/s41422-018-0040-8
3 BODI Z, BUTTON J D, GRIERSON D, et al. Yeast targets for mRNA methylation. Nucleic Acids Research, 2010,38(16):5327-5335. DOI:10.1093/nar/gkq266
doi: 10.1093/nar/gkq266
4 KENNEDY T D, LANE B G. Wheat embryo ribonucleates. XIII. Methyl-substituted nucleoside constituents and 5′-terminal dinucleotide sequences in bulk poly(AR)-rich RNA from imbibing wheat embryos. Canadian Journal of Biochemistry, 1979,57(6):927-931.
5 HONGAY C F, ORR-WEAVER T L. Drosophila inducer of MEiosis 4 (IME4) is required for Notch signaling during oogenesis. PNAS, 2011,108(36):14855-14860. DOI:10.1073/pnas.1111577108
doi: 10.1073/pnas.1111577108
6 YOON K J, RINGELING F R, VISSERS C, et al. Temporal control of mammalian cortical neurogenesis by m6A methylation. Cell, 2017,171(4):877-889. DOI:10.1016/j.cell.2017.09.003
doi: 10.1016/j.cell.2017.09.003
7 XIAO W, ADHIKARI S, DAHAL U, et al. Nuclear m6A reader YTHDC1 regulates mRNA splicing. Molecular Cell, 2016,61(4):507-519. DOI:10.1016/j.molcel.2016.01.012
doi: 10.1016/j.molcel.2016.01.012
8 ROUNDTREE I A, LUO G Z, ZHANG Z J, et al. YTHDC1 mediates nuclear export of N 6-methyladenosine methylated mRNAs. eLife, 2017,6:e31311. DOI:10.7554/eLife.31311
doi: 10.7554/eLife.31311
9 LI A, CHEN Y S, PING X L, et al. Cytoplasmic m6A reader YTHDF3 promotes mRNA translation. Cell Research, 2017,27(3):444-447. DOI:10.1038/cr.2017.10
doi: 10.1038/cr.2017.10
10 WANG X, LU Z K, GOMEZ A, et al. m6A-dependent regulation of messenger RNA stability. Nature, 2014,505(7481):117-120. DOI:10.1038/nature12730
doi: 10.1038/nature12730
11 HSU P J, SHI H L, HE C. Epitranscriptomic influences on development and disease. Genome Biology, 2017,18(1):197. DOI:10.1186/s13059-017-1336-6
doi: 10.1186/s13059-017-1336-6
12 DESROSIERS R, FRIDERICI K, ROTTMAN F. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. PNAS, 1974,71(10):3971-3975.
13 DOMINISSINI D, MOSHITCH-MOSHKOVITZ S, SCHWARTZ S, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature, 2012,485(7397):201-206. DOI:10.1038/nature11112
doi: 10.1038/nature11112
14 MEYER K D, SALETORE Y, ZUMBO P, et al. Comprehensive analysis of mRNA methylation reveals enrichment in 3′UTRs and near stop codons. Cell, 2012,149(7):1635-1646. DOI:10.1016/j.cell.2012.05.003
doi: 10.1016/j.cell.2012.05.003
15 CHEN K, LU Z K, WANG X, et al. High-resolution N 6-methyladenosine (m6A) map using photo-crosslinking-assisted m6A sequencing. Angewandte Chemie: International Edition, 2015,54(5):1587-1590. DOI:10.1002/anie.201410647
doi: 10.1002/anie.201410647
16 LENCE T, SOLLER M, ROIGNANT J Y. A fly view on the roles and mechanisms of the m6A mRNA modification and its players. RNA Biology, 2017,14(9):1232-1240. DOI:10.1080/15476286.2017.1307484
doi: 10.1080/15476286.2017.1307484
17 BOKAR J A, SHAMBAUGH M E, POLAYES D, et al. Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N 6-adenosine)-methyltrans-ferase. RNA, 1997,3(11):1233-1247.
18 HAUSSMANN I U, BODI Z, SANCHEZ-MORAN E, et al. m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature, 2016,540(7632):301-304. DOI:10.1038/nature20577
doi: 10.1038/nature20577
19 JIANG T, LI J S, QIAN P, et al. The role of N 6-methyladenosine modification on diapause in silkworm (Bombyx mori) strains that exhibit different voltinism. Molecular Reproduction and Development, 2019,86(12):1981-1992. DOI:10.1002/mrd.23283
doi: 10.1002/mrd.23283
20 LIU J Z, YUE Y N, HAN D L, et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N 6-adenosine methylation. Nature Chemical Biology, 2014,10(2):93-95. DOI:10.1038/nchembio.1432
doi: 10.1038/nchembio.1432
21 HORIUCHI K, KAWAMURA T, IWANARI H, et al. Identification of Wilms’ tumor 1-associating protein complex and its role in alternative splicing and the cell cycle. The Journal of Biological Chemistry, 2013,288(46):33292-33302. DOI:10.1074/jbc.M113.500397
doi: 10.1074/jbc.M113.500397
22 RAFFEL G D, CHU G C, JESNECK J L, et al. Ott1 (Rbm15) is essential for placental vascular branching morphogenesis and embryonic development of the heart and spleen. Molecular and Cellular Biology, 2009,29(2):333-341. DOI:10.1128/MCB.00370-08
doi: 10.1128/MCB.00370-08
23 BOKAR J A, RATH-SHAMBAUGH M E, LUDWICZAK R, et al. Characterization and partial purification of mRNA N 6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex. The Journal of Biological Chemistry, 1994,269(26):17697-17704.
24 WANG X, FENG J, XUE Y, et al. Structural basis of N 6-adenosine methylation by the METTL3-METTL14 complex. Nature, 2016,534(7608):575-578. DOI:10.1038/nature18298
doi: 10.1038/nature18298
25 PING X L, SUN B F, WANG L, et al. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Research, 2014,24(2):177-189. DOI:10.1038/cr.2014.3
doi: 10.1038/cr.2014.3
26 YUE Y N, LIU J, CUI X L, et al. VIRMA mediates preferential m6A mRNA methylation in 3′UTR and near stop codon and associates with alternative polyadenylation. Cell Discovery, 2018,4:10. DOI:10.1038/s41421-018-0019-0
doi: 10.1038/s41421-018-0019-0
27 JIA G F, FU Y, ZHAO X, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nature Chemical Biology, 2011,7(12):885-887. DOI:10.1038/nchembio.687
doi: 10.1038/nchembio.687
28 ZHENG G O, DAHL J A, NIU Y M, et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Molecular Cell, 2013,49(1):18-29. DOI:10.1016/j.molcel.2012.10.015
doi: 10.1016/j.molcel.2012.10.015
29 GERKEN T, GIRARD C A, TUNG L Y C, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science, 2007,318(5855):1469-1472. DOI:10.1126/science.1151710
doi: 10.1126/science.1151710
30 ZHANG Z, THELER D, KAMINSKA K H, et al. The YTH domain is a novel RNA binding domain. The Journal of Biological Chemistry, 2010,285(19):14701-14710. DOI:10.1074/jbc.M110.104711
doi: 10
31 ROUNDTREE I A, HE C. Nuclear m6A reader YTHDC1 regulates mRNA splicing. Trends in Genetics, 2016,32(6):320-321. DOI:10.1016/j.tig.2016.03.006
doi: 10.1016/j.tig.2016.03.006
32 DU H, ZHAO Y, HE J Q, et al. YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nature Communications, 2016,7:12626. DOI:10.1038/ncomms12626
doi: 10.1038/ncomms12626
33 SHI H L, WANG X, LU Z K, et al. YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA. Cell Research, 2017,27(3):315-328. DOI:10.1038/cr.2017.15
doi: 10.1038/cr.2017.15
34 JAIN D, PUNO M R, MEYDAN C, et al. ketu mutant mice uncover an essential meiotic function for the ancient RNA helicase YTHDC2. eLife, 2018,7:e30919. DOI:10.7554/eLife.30919
doi: 10.7554/eLife.30919
35 KAN L, GROZHIK A V, VEDANAYAGAM J, et al. The m6A pathway facilitates sex determination in Drosophila. Nature Communications, 2017,8:15737. DOI:10.1038/ncomms15737
doi: 10.1038/ncomms15737
36 LI B, WANG X, LI Z, et al. Transcriptome-wide analysis of N6-methyladenosine uncovers its regulatory role in gene expression in the lepidopteran Bombyx mori. Insect Molecular Biology, 2019,28(5):703-715. DOI:10.1111/imb.12584
doi: 10.1111/imb.12584
37 ZHANG X, ZHANG Y S, DAI K, et al. N6-methyladenosine level in silkworm midgut/ovary cell line is associated with Bombyx mori nucleopolyhedrovirus infection. Frontiers in Microbiology, 2019,10:2988. DOI:10.3389/fmicb.2019.02988
doi: 10.3389/fmicb.2019.02988
38 BELL L R, HORABIN J I, SCHEDL P, et al. Positive autoregulation of sex-lethal by alternative splicing maintains the female determined state in Drosophila. Cell, 1991,65(2):229-239. DOI:10.1016/0092-8674(91)90157-t
doi: 10.1016/0092-8674(91)90157-t
39 GUO J, TANG H W, LI J, et al. Xio is a component of the Drosophila sex determination pathway and RNA N6-methyladenosine methyltransferase complex. PNAS, 2018,115(14):3674-3679. DOI:10.1073/pnas.1720945115
doi: 10.1073/pnas.1720945115
40 LENCE T, AKHTAR J, BAYER M, et al. m6A modulates neuronal functions and sex determination in Drosophila. Nature, 2016,540(7632):242-247. DOI:10.1038/nature20568
doi: 10.1038/nature20568
41 GRANADINO B, CAMPUZANO S, SáNCHEZ L. The Drosophilamelanogasterfl(2)d gene is needed for the female-specific splicing of Sex-lethal RNA. The EMBO Journal, 1990,9(8):2597-2602.
42 ANDERSON A M, WEASNER B P, WEASNER B M, et al. The Drosophila Wilms’ tumor 1-associating protein (WTAP) homolog is required for eye development. Developmental Biology, 2014,390(2):170-180. DOI:10.1016/j.ydbio.2014.03.012
doi: 10.1016/j.ydbio.2014.03.012
43 CHANG L J L, LIN H V, BLAUWKAMP T A, et al. Spenito and split ends act redundantly to promote wingless signaling. Developmental Biology, 2008,314(1):100-111. DOI:10.1016/j.ydbio.2007.11.023
doi: 10.1016/j.ydbio.2007.11.023
44 YAN D, PERRIMON N. Spenito is required for sex determination in Drosophila melanogaster. PNAS, 2015,112(37):11606-11611. DOI:10.1073/pnas.1515891112
doi: 10.1073/pnas.1515891112
45 LUCCHESI J C, KURODA M I. Dosage compensation in Drosophila. Cold Spring Harbor Perspectives in Biology, 2015,7(5):a019398. DOI:10.1101/cshperspect.a019398
doi: 10.1101/cshperspect.a019398
46 GEULA S, MOSHITCH-MOSHKOVITZ S, DOMINISSINI D, et al. Stem cells. m6A mRNA methylation facilitates resolution of na?ve pluripotency toward differentiation. Science, 2015,347(6225):1002-1006. DOI:10.1126/science.1261417
doi: 10.1126/science.1261417
47 LUO G Z, MACQUEEN A, ZHENG G, et al. Unique features of the m6A methylome in Arabidopsisthaliana. Nature Communications, 2014,5:5630. DOI: 10.1038/ncomms6630
doi: 10.1038/ncomms6630
48 ZHAO B S, WANG X, BEADELL A V, et al. m6A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition. Nature, 2017,542(7642):475-478. DOI:10.1038/nature21355
doi: 10.1038/nature21355
49 KNUCKLES P, LENCE T, HAUSSMANN I U, et al. Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d. Genes & Development, 2018,32(5/6):415-429. DOI:10.1101/gad.309146.117
doi: 10.1101/gad.309146.117
50 PENDLETON K E, CHEN B B, LIU K Q, et al. The U6 snRNA m6A methyltransferase METTL16 regulates SAM synthetase intron retention. Cell, 2017,169(5):824-835. DOI:10.1016/j.cell.2017.05.003
doi: 10.1016/j.cell.2017.05.003
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