Abstract
RNA modifications play an essential role in determining RNA fate. Recent studies have revealed the effects of such modifications on all steps of RNA metabolism. These modifications range from the addition of simple groups, such as methyl groups, to the addition of highly complex structures, such as sugars. Their consequences for translation fidelity are not always well documented. Unlike the well-known m6A modification, they are thought to have direct effects on either the folding of the molecule or the ability of tRNAs to bind their codons. Here we describe how modifications found in tRNAs anticodon-loop, rRNA, and mRNA can affect translation fidelity, and how approaches based on direct manipulations of the level of RNA modification could potentially be used to modulate translation for the treatment of human genetic diseases.
Highlights
All types of RNA are subject to post-transcriptional modification
We mainly focus on the importance of RNA modifications in the two most abundant noncoding RNA families and their consequences for translation fidelity
There is a striking difference in the mode of action of modifications between coding and non-coding RNAs, in that modifications to rRNAs and tRNAs act directly on the folding and activity of the molecule, whereas most of the modifications to mRNAs act via reader proteins
Summary
All types of RNA are subject to post-transcriptional modification. Since the discovery of RNA modifications in 1951, more than 150 RNA modifications have been found in coding and non-coding RNAs ranging from the addition of simple groups to the addition of highly complex structures (Figure 1) [1,2,3]. There is a striking difference in the mode of action of modifications between coding and non-coding RNAs, in that modifications to rRNAs and tRNAs act directly on the folding and activity of the molecule, whereas most of the modifications to mRNAs act via reader proteins. This simplified presentation needs to be modulated because some tRNA modifications are required for the proper action of aminoacyl-tRNA synthetases (aaRS) [29]
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