Abstract
Ribosomal RNA (rRNA) is extensively edited through base methylation and acetylation, 2′-O-ribose methylation and uridine isomerization. In human rRNA, 95 uridines are predicted to by modified to pseudouridine by ribonucleoprotein complexes sharing four core proteins and differing for a RNA sequence guiding the complex to specific residues to be modified. Most pseudouridylation sites are placed within functionally important ribosomal domains and can influence ribosomal functional features. Information obtained so far only partially explained the degree of regulation and the consequences of pseudouridylation on ribosomal structure and function in different physiological and pathological conditions. This short review focuses on the available evidence in this topic, highlighting open questions in the field and perspectives that the development of emerging techniques is offering.
Highlights
Most interactions between pre-Ribosomal RNA (rRNA) and pseudouridylation RNP complexes may occur transcriptionally; in yeast it has been shown that pre‐ rRNA transcripts are first completed co-transcriptionally; in yeast it has been shown that pre- rRNA transcripts are first completed and modified before further processing, probably because modifications are required for the and modified before further processing, probably because modifications are required for the acquisition acquisition of structural conformations necessary for the occurrence of later processing events [13]
DKC1 gene have been reported in familial interstitial pneumonia [32]. In addition to these inherited disorders, a subset of human cancers arising in the general population display reduced dyskerin expression and functions and low rRNA pseudouridylation suggesting that the observed translational defects may contribute to the neoplastic phenotype in a fraction of sporadic tumors [31,33]
The impact of the presence/absence of a single modification or combinations of a limited number of modifications has been explored only in yeast, and the scientific community currently has limited information on how this could be important in regulating mammalian ribosome function, protein synthesis, and gene expression in different physiological states and in many human disorders
Summary
Pseudouridine (Ψ) is the 5-ribosyl isomer of uridine (Figure 1). It derives from the uracil base rotation of 180◦ , which makes the uracil attached to the 10 carbon (C1 ́) of the ribose via a carbon-carbon instead of a nitrogen-carbon glycosidic bond (see [1,2] for a broader review). Most interactions between pre-rRNA and pseudouridylation RNP complexes may occur transcriptionally; in yeast it has been shown that pre‐ rRNA transcripts are first completed co-transcriptionally; in yeast it has been shown that pre- rRNA transcripts are first completed and modified before further processing, probably because modifications are required for the and modified before further processing, probably because modifications are required for the acquisition acquisition of structural conformations necessary for the occurrence of later processing events [13] On this regard, On this regard, it is not definitively clear each of the of predicted snoRNA events guided[13]. Associations it is not definitively clear if each of the predicted snoRNA guided associations require the Biomolecules 2018, 8, 38 modification to occur or if instead, in some cases, the molecular interaction is sufficient to allow for the processing
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