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Review
. 2019 Apr 26;476(8):1227-1245.
doi: 10.1042/BCJ20180445.

The chemical diversity of RNA modifications

R Jordan Ontiveros  1 , Julian Stoute  1 , Kathy Fange Liu  2
Affiliations
Review

The chemical diversity of RNA modifications

R Jordan Ontiveros et al. Biochem J. .

Abstract

Nucleic acid modifications in DNA and RNA ubiquitously exist among all the three kingdoms of life. This trait significantly broadens the genome diversity and works as an important means of gene transcription regulation. Although mammalian systems have limited types of DNA modifications, over 150 different RNA modification types have been identified, with a wide variety of chemical diversities. Most modifications occur on transfer RNA and ribosomal RNA, however many of the modifications also occur on other types of RNA species including mammalian mRNA and small nuclear RNA, where they are essential for many biological roles, including developmental processes and stem cell differentiation. These post-transcriptional modifications are enzymatically installed and removed in a site-specific manner by writer and eraser proteins respectively, while reader proteins can interpret modifications and transduce the signal for downstream functions. Dysregulation of mRNA modifications manifests as disease states, including multiple types of human cancer. In this review, we will introduce the chemical features and biological functions of these modifications in the coding and non-coding RNA species.

Keywords: RNA modification; chemical property; mRNA; non-coding RNA; rRNA; tRNA.

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Figures

Figure 1.
Figure 1.
Transfer RNA secondary and tertiary structure. (A) Two-dimensional clover-leaf structure and the five domains that make up a tRNA. Specific residues whose modifications are discussed in this review are denoted. (B) Three-dimensional structure of tRNA (PDB code: 1YFG). The color code of the two-dimensional structure matches with that of the three-dimensional structure.
Figure 2.
Figure 2.
The chemical structures of nucleoside and ribose modifications addressed in this review. (A) Adenosine and its modified derivatives. (B) Guanosine and its modified derivatives. (C) Uridine and its modified derivatives. (D) Cytosine and its modified derivatives. (E) Modified 2′-O-methylribose. (F) Chair representations of ribose sugar pucker 2′ and 3′ endo conformations. B = base. R = ribose
Figure 3.
Figure 3.
The chemical structure of a canonical Watson-Crick base pairing between G and C (left) and the reverse Watson-Crick base pairing between G48 and C15 which form the Levitt pair (right).
Figure 4.
Figure 4.
Modifications and proteins related to mRNA modifications. Diagramed from the left is the 5′ cap structure consisting of m7G, ribose sugar, and the 5′ to 5′ triphosphate linkage. Following this are the five internal mRNA modification structures as well as their related writers (green), erasers (purple) and readers (blue) described in this review listed in columns below. An = Polyadenylated tail.
See this image and copyright information in PMC

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