Abstract
Ribosomal RNA (rRNA) from all organisms undergoes post-transcriptional modifications that increase the diversity of its composition and activity. In mitochondria, specialized mitochondrial ribosomes (mitoribosomes) are responsible for the synthesis of 13 oxidative phosphorylation proteins encoded by the mitochondrial genome. Mitoribosomal RNA is also modified, with 10 modifications thus far identified and all corresponding modifying enzymes described. This form of epigenetic regulation of mitochondrial gene expression affects mitoribosome biogenesis and function. Here, we provide an overview on rRNA methylation and highlight critical work that is beginning to elucidate its role in mitochondrial gene expression. Given the similarities between bacterial and mitochondrial ribosomes, we focus on studies involving Escherichia coli and human models. Furthermore, we highlight the use of state-of-the-art technologies, such as cryoEM in the study of rRNA methylation and its biological relevance. Understanding the mechanisms and functional relevance of this process represents an exciting frontier in the RNA biology and mitochondrial fields.
Highlights
We provide an overview on Ribosomal RNA (rRNA) methylation and highlight critical work that is beginning to elucidate its role in mitochondrial gene expression
Given the similarities between bacterial and mitochondrial ribosomes, we focus on studies involving Escherichia coli and human models
There is a growing list of human genetic disorders named ribosomopathies that are caused by mutations in genes encoding ribosomal proteins or ribosome biogenesis cofactors, including those involved in the rRNA methylation machinery
Summary
RNA modifications are present in all living organisms and play important roles in RNA metabolism. RNA modifications are predominantly found in transfer RNA (tRNA), with modifications identified in up to 20% of nucleotides (Jackman and Alfonzo, 2013). Not as common as in tRNA, human cytosolic ribosomal RNA (rRNA) contains 14 distinct types of post-transcriptional modifications in 228 sites (Taoka et al, 2018), while Escherichia coli rRNAs contain 36 modified nucleotides (Sergiev et al, 2011). Among the different types of rRNA modifications, 2′-O-methylation of the ribose followed by pseudouridylation is the most common (for a review on this abundant RNA modification see Charette and Gray, 2000). The introduction of rRNA modifications is closely linked to rRNA processing events and coupled to various stages of ribosome assembly (Armistead et al, 2009; Bourgeois et al, 2015; Zorbas et al, 2015)
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