Abstract
RNA modifications are essential for proper RNA processing, quality control, and maturation steps. In the last decade, some eukaryotic DNA repair enzymes have been shown to have an ability to recognize and process modified RNA substrates and thereby contribute to RNA surveillance. Single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1) is a base excision repair enzyme that not only recognizes and removes uracil and oxidized pyrimidines from DNA but is also able to process modified RNA substrates. SMUG1 interacts with the pseudouridine synthase dyskerin (DKC1), an enzyme essential for the correct assembly of small nucleolar ribonucleoproteins (snRNPs) and ribosomal RNA (rRNA) processing. Here, we review rRNA modifications and RNA quality control mechanisms in general and discuss the specific function of SMUG1 in rRNA metabolism. Cells lacking SMUG1 have elevated levels of immature rRNA molecules and accumulation of 5-hydroxymethyluridine (5hmU) in mature rRNA. SMUG1 may be required for post-transcriptional regulation and quality control of rRNAs, partly by regulating rRNA and stability.
Highlights
A wide variety of functional base modifications are present in cellular RNA in addition to the regular four ribonucleosides
RNA molecules distinguished from damaged RNA molecules? Little is known about how cellular pathways manage to discriminate between these, in principle, different RNA modifications
DNA repair enzymes have emerged as factors in RNA metabolism, especially in ribosomal RNA (rRNA) biogenesis
Summary
A wide variety of functional base modifications are present in cellular RNA in addition to the regular four ribonucleosides. Over 160 known chemical modifications that modulate the structure and function of RNA molecules have been described [1,2,3,4,5,6,7]. RNAs. all RNA classes, including messenger (mRNAs) and small nuclear RNAs, contain base modifications. Base modifications introduced enzymatically at defined positions change RNA function at several levels. We will first give an overview of the main rRNA modifications and RNA quality control mechanisms and discuss recent developments implicating the SMUG1 DNA-glycosylase in rRNA biogenesis. 5-hydroxylmethyluridine (hm5U), a base modification recognized by SMUG1, pointing to SMUG1 as a possible new enzyme involved in the regulation of rRNA.
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