Received date: 2013-04-28
Revised date: 2013-08-25
Online published: 2013-11-21
RNA modifications, especially methylation of the N6 position of adenosine (A)––m6A, represent an emerging research territory in RNA biology. m6A is a post-transcriptional modification of RNAs, which is catalyzed by the mRNA: m6A methyltransferase complex containing three individual components and is the most common form found in the internal se-quences of mRNAs in eukaryotes. Latest study showed that the fat mass and obesity-associated protein could remove the methyl group, indicating that the modification is reversible. Importantly, inhibiting or silencing the methyltransferase will cause significant changes of phenotypes. However, due to limited detection methods, the mechanism of m6A has not been figured out yet. Next-generation sequencing combining with IP (immunoprecipitation) technologies makes it possible to detect m6A modifications in a large scale. Here, we reviewed recent progresses of m6A studies including the discovery of m6A, mechanism of biosynthesis, tissue and genome distribution, detection methodology and possible biological functions. We also compared three IP-seq technologies that are currently widely used, and summarized the challenges in m6A studies.
Key words： RNA modifications; m6A; IP-seq
LI Yu-Li, YU Jun, SONG Shu-Hui . Recent progresses in RNA N6-methyladenosine research[J]. Hereditas(Beijing), 2013 , 35(12) : 1340 -1351 . DOI: 10.3724/SP.J.1005.2013.01340
[1] Sharp PA.The Centrality of RNA. Cell, 2009, 136(4): 577–580.
[2] Cantara WA, Crain PF, Rozenski J, McCloskey JA, Harris KA, Zhang X, Vendeix FAP, Fabris D, Agris PF. The RNA modification database, RNAMDB: 2011 update. Nucleic Acids Res, 2010, 39(Database): D195–D201.
[3] Dunn DB, Smith JD. Occurrence of a new base in the deoxyribonucleic acid of a strain of Bacterium Coli. Nature, 1955, 175(4451): 336–337.
[4] Dunn DB, Smith JD. The occurrence of 6-methylaminopurine in deoxyribonucleic acids. Biochem J, 1958, 68(4): 627–636.
[5] Littlefield JW, Dunn DB. Natural occurrence of thymine and three methylated adenine bases in several ribonucleic acids. Nature, 1958, 181(4604): 254–255.
[6] Jelinek W, Adesnik M, Salditt M, Sheiness D, Wall R, Molloy G, Philipson L, Darnell JE. Further evidence on the nuclear origin and transfer to the cytoplasm of polyadenylic acid sequences in mammalian cell RNA. J Mol Biol, 1973, 75(3): 515–532.
[7] Desrosie R, Frideric K, Rottman F. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc Natl Acad Sci USA, 1974, 71(10): 3971–3975.
[8] Adams JM, Cory S. Modified nucleosides and bizarre 5′-termini in mouse myeloma mRNA. Nature, 1975, 255(5503): 28–33.
[9] Desrosiers RC, Friderici KH, Rottman FM. Characterization of Novikoff hepatoma mRNA methylation and heterogeneity in the methylated 5' terminus. Biochemistry, 1975, 14(20): 4367–4374.
[10] Dubin DT, Taylor RH. The methylation state of poly A-containing-messenger RNA from cultured hamster cells. Nucleic Acids Res, 1975, 2(10): 1653–1668.
[11] Furuichi Y, Morgan M, Muthukrishnan S, Shatkin AJ. Reovirus messenger RNA contains a methylated, blocked 5′-terminal structure: m-7G(5′)ppp(5′)G-MpCp-. Proc Natl Acad Sci USA, 1975, 72(1): 362–366.
[12] Perry RP, Kelley DE, Friderici K, Rottman F. The methylated constituents of L cell messenger RNA: evidence for an unusual cluster at the 5′ terminus. Cell, 1975, 4(4): 387–394.
[13] Haugland RA, Cline MG. Post-transcriptional modifications of oat coleoptile ribonucleic acids. 5′-Terminal capping and methylation of internal nucleosides in poly(A)- rich RNA. Eur J Biochem, 1980, 104(1): 271–277.
[14] Beemon K, Keith J. Localization of N6-methyladenosine in the Rous sarcoma virus genome. J Mol Biol, 1977, 113(1): 165–179.
[15] Moss B, Gershowitz A, Stringer JR, Holland LE, Wagner EK. 5′-Terminal and internal methylated nucleosides in herpes simplex virus type 1 mRNA. J Virol, 1977, 23(2): 234–239.
[16] Chen-Kiang S, Nevins JR, Darnell JE Jr. N-6-methyl- adenosine in adenovirus type 2 nuclear RNA is conserved in the formation of messenger RNA. J Mol Biol, 1979, 135(3): 733–752.
[17] Narayan P, Rottman FM. An in vitro system for accurate methylation of internal adenosine residues in messenger RNA. Science, 1988, 242(4882): 1159–1162.
[18] Tuck MT. Partial purification of a 6-methyladenine mRNA methyltransferase which modifies internal adenine residues. Biochem J, 1992, 288(Pt 1): 233–240.
[19] Bokar JA, Rath-Shambaugh ME, Ludwiczak R, Narayan P, Rottman F. Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex. J Biol Chem, 1994, 269(26): 17697–17704.
[20] Bokar JA, Shambaugh ME, Polayes D, Matera AG, Rottman FM. Purification and cDNA cloning of the AdoMet- binding subunit of the human mRNA (N6-adenosine)- methyltransferase. RNA, 1997, 3(11): 1233–1247.
[21] Bujnicki JM, Feder M, Radlinska M, Blumenthal RM. Structure prediction and phylogenetic analysis of a functionally diverse family of proteins homologous to the MT-A70 subunit of the human mRNA:m(6)A
/
| 〈 |
|
〉 |
www.chinagene.cn
备案号：京ICP备09063187号
