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RNA modifications – an overview
The field of epigenetics is branching down many new and exciting avenues. One of these avenues is the area of RNA modification research. Recent advancements in the development of RNA modification detection and sequencing methods, such as miCLIP, have meant that it is becoming easier and faster to discover new modifications and map them to different RNA species within any cell type or model organism. The advancements in this technology lead to a boom in the number of known RNA modifications. There are currently over 100 known RNA chemical modifications, including m6A, m1A, ac4C, and m2,2G1. You find these on mRNA, tRNAs, rRNAs, and other non-coding RNAs, including miRNAs. Each of these modifications also has its own functions, including RNA structure, export, stability, and mRNA splicing. The future is bright for this research field; there is still much to uncover about the function of some of these new exciting modifications.
RNA modifications in mRNAs
You can find several RNA modifications within mRNAs, and some are even known to have essential functions. The presence of an RNA modification within mRNA may act in several different ways, including altering RNA structure, promoting RNA-protein binding, and changing RNA charge or base pairing potential. m6A is one of the most abundant modifications within mRNA, where it is known to have a plethora of functions, including aiding mRNA splicing2, structural switching3, stability4, and translation efficiency5. To find out more, check out our m6A pathway and functions poster here.
RNA modifications in tRNAs
Of all the RNA species, tRNAs contain the most RNA modifications. Almost one in five nucleotides within tRNAs are thought to contain RNA modifications6. The modifications on tRNA are incredibly diverse. Some modifications require step-by-step formation by multiple enzymes7. You can commonly find modifications in the anticodon loop of the tRNA. These are found here to help promote translation efficiency by aiding codon-anticodon interactions and preventing frameshifting8.
1)Roundtree, I., Evans, M., Pan, T., & He, C. (2017) Dynamic RNA Modifications in Gene Expression Regulation. Cell, 1187-1200
2) Xiao, W., Adhikari, S., Dahal, U., Chen, Y.S., Hao, Y.J., Sun, B.F., Sun, H.Y., Li, A., Ping, X.L., Lai, W.Y., et al. (2016). Nuclear m6A Reader YTHDC1 Regulates mRNA Splicing. Mol. Cell 61, 507–519.
3) Liu, N., Dai, Q., Zheng, G., He, C., Parisien, M., and Pan, T. (2015). N6-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature 518, 560–564.
4) Du, H., Zhao, Y., He, J., Zhang, Y., Xi, H., Liu, M., Ma, J., and Wu, L. (2016). YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4–NOT deadenylase complex. Nat. Commun. 7, 12626.
5) Wang, X., Zhao, B.S., Roundtree, I.A., Lu, Z., Han, D., Ma, H., Weng, X., Chen, K., Shi, H., and He, C. (2015). N6-methyladenosine modulates messenger RNA translation efficiency. Cell 161, 1388–1399.
6) Kirchner, S., and Ignatova, Z. (2015). Emerging roles of tRNA in adaptive translation, signaling dynamics and disease. Nat. Rev. Genet. 16, 98–112.
7) Rubio, M.A.T., Gaston, K.W., McKenney, K.M., Fleming, I.M.C., Paris, Z., Limbach, P.A., and Alfonzo, J.D. (2017). Editing and methylation at a single site by functionally interdependent activities. Nature 542, 494–497.
8) Stuart, J.W., Koshlap, K.M., Guenther, R., and Agris, P.F. (2003). Naturally occurring modification restricts the anticodon domain conformational space of tRNA (Phe). J. Mol. Biol. 334, 901–918.