Translating the Epitranscriptome

Overview

Journal Wiley Interdiscip Rev RNA

Publisher Wiley

Date 2016 Jun 28

PMID 27345446

Citations 27

Authors

Thomas Philipp Hoernes

Matthias David Erlacher

Affiliations

Soon will be listed here.

Abstract

RNA modifications are indispensable for the translation machinery to provide accurate and efficient protein synthesis. Whereas the importance of transfer RNA (tRNA) and ribosomal RNA (rRNA) modifications has been well described and is unquestioned for decades, the significance of internal messenger RNA (mRNA) modifications has only recently been revealed. Novel experimental methods have enabled the identification of thousands of modified sites within the untranslated and translated regions of mRNAs. Thus far, N -methyladenosine (m A), pseudouridine (Ψ), 5-methylcytosine (m C) and N -methyladenosine (m A) were identified in eukaryal, and to some extent in prokaryal mRNAs. Several of the functions of these mRNA modifications have previously been reported, but many aspects remain elusive. Modifications can be important factors for the direct regulation of protein synthesis. The potential diversification of genomic information and regulation of RNA expression through editing and modifying mRNAs is versatile and many questions need to be addressed to completely elucidate the role of mRNA modifications. Herein, we summarize and highlight some recent findings on various co- and post-transcriptional modifications, describing the impact of these processes on gene expression, with emphasis on protein synthesis. WIREs RNA 2017, 8:e1375. doi: 10.1002/wrna.1375 For further resources related to this article, please visit the WIREs website.

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References

Tomita K, Ueda T, Watanabe K . The presence of pseudouridine in the anticodon alters the genetic code: a possible mechanism for assignment of the AAA lysine codon as asparagine in echinoderm mitochondria. Nucleic Acids Res. 1999; 27(7):1683-9. PMC: 148372. DOI: 10.1093/nar/27.7.1683. View

Chen J, Patton J . Cloning and characterization of a mammalian pseudouridine synthase. RNA. 1999; 5(3):409-19. PMC: 1369769. DOI: 10.1017/s1355838299981591. View

Zebarjadian Y, King T, Fournier M, Clarke L, Carbon J . Point mutations in yeast CBF5 can abolish in vivo pseudouridylation of rRNA. Mol Cell Biol. 1999; 19(11):7461-72. PMC: 84741. DOI: 10.1128/MCB.19.11.7461. View

Helm M, Giege R, Florentz C . A Watson-Crick base-pair-disrupting methyl group (m1A9) is sufficient for cloverleaf folding of human mitochondrial tRNALys. Biochemistry. 1999; 38(40):13338-46. DOI: 10.1021/bi991061g. View

Warner J . The economics of ribosome biosynthesis in yeast. Trends Biochem Sci. 1999; 24(11):437-40. DOI: 10.1016/s0968-0004(99)01460-7. View

Madore E, Florentz C, Giege R, Sekine S, Yokoyama S, Lapointe J . Effect of modified nucleotides on Escherichia coli tRNAGlu structure and on its aminoacylation by glutamyl-tRNA synthetase. Predominant and distinct roles of the mnm5 and s2 modifications of U34. Eur J Biochem. 1999; 266(3):1128-35. DOI: 10.1046/j.1432-1327.1999.00965.x. View

Chen C, Cho D, Wang Q, Lai F, Carter K, Nishikura K . A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single- and double-stranded RNA binding domains. RNA. 2000; 6(5):755-67. PMC: 1369955. DOI: 10.1017/s1355838200000170. View

Hickey A, Macario A, Conway de Macario E . Identification of genes in the genome of the archaeon Methanosarcina mazeii that code for homologs of nuclear eukaryotic molecules involved in RNA processing. Gene. 2000; 253(1):77-85. DOI: 10.1016/s0378-1119(00)00235-3. View

Maas S, Rich A . Changing genetic information through RNA editing. Bioessays. 2000; 22(9):790-802. DOI: 10.1002/1521-1878(200009)22:9<790::AID-BIES4>3.0.CO;2-0. View

10.

Gott J, Emeson R . Functions and mechanisms of RNA editing. Annu Rev Genet. 2000; 34:499-531. DOI: 10.1146/annurev.genet.34.1.499. View

11.

Cavaille J, Buiting K, Kiefmann M, Lalande M, Brannan C, Horsthemke B . Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. Proc Natl Acad Sci U S A. 2000; 97(26):14311-6. PMC: 18915. DOI: 10.1073/pnas.250426397. View

12.

Adams J, Cory S . Modified nucleosides and bizarre 5'-termini in mouse myeloma mRNA. Nature. 1975; 255(5503):28-33. DOI: 10.1038/255028a0. View

13.

Huttenhofer A, Kiefmann M, OBrien J, Lehrach H, Bachellerie J, Brosius J . RNomics: an experimental approach that identifies 201 candidates for novel, small, non-messenger RNAs in mouse. EMBO J. 2001; 20(11):2943-53. PMC: 125495. DOI: 10.1093/emboj/20.11.2943. View

14.

Zhang Z, Carmichael G . The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs. Cell. 2001; 106(4):465-75. DOI: 10.1016/s0092-8674(01)00466-4. View

15.

DUBIN D, Taylor R . The methylation state of poly A-containing messenger RNA from cultured hamster cells. Nucleic Acids Res. 1975; 2(10):1653-68. PMC: 343535. DOI: 10.1093/nar/2.10.1653. View

16.

DUBIN D, Stollar V . Methylation of Sindbis virus "26S" messenger RNA. Biochem Biophys Res Commun. 1975; 66(4):1373-9. DOI: 10.1016/0006-291x(75)90511-2. View

17.

Darzacq X, Jady B, Verheggen C, Kiss A, Bertrand E, Kiss T . Cajal body-specific small nuclear RNAs: a novel class of 2'-O-methylation and pseudouridylation guide RNAs. EMBO J. 2002; 21(11):2746-56. PMC: 126017. DOI: 10.1093/emboj/21.11.2746. View

18.

Bujnicki J, Feder M, Radlinska M, Blumenthal R . 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 methyltransferase. J Mol Evol. 2002; 55(4):431-44. DOI: 10.1007/s00239-002-2339-8. View

19.

Byrne E, Gott J . Cotranscriptional editing of Physarum mitochondrial RNA requires local features of the native template. RNA. 2002; 8(9):1174-85. PMC: 1370331. DOI: 10.1017/s1355838202024081. View

20.

Clancy M, Shambaugh M, Timpte C, Bokar J . Induction of sporulation in Saccharomyces cerevisiae leads to the formation of N6-methyladenosine in mRNA: a potential mechanism for the activity of the IME4 gene. Nucleic Acids Res. 2002; 30(20):4509-18. PMC: 137137. DOI: 10.1093/nar/gkf573. View