RNA Metabolism Guided by RNA Modifications: The Role of SMUG1 in rRNA Quality Control

Lirussi, Lisa; Demir, Özlem; You, Panpan; Sarno, Antonio; Amaro, Rommie E.; Nilsen, Hilde

doi:10.3390/biom11010076

Cited by 8 publications

(7 citation statements)

References 178 publications

(180 reference statements)

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“…Similar to cellular DNA, RNA is also extensively chemically modified, and such modifications occur on all types of RNAs and influence all aspects of RNA metabolism, increasing the complexity of RNA regulation [ 63 , 64 , 65 , 66 , 67 , 68 ]. RNA is highly susceptible and reactive to oxidation, and numerous oxidized RNA modifications are formed such as 8-oxoguanine (o 8 G), 8-oxoadenine (o 8 A), 5-hydroxyuridine, and 5-hydroxycytidine [ 61 , 69 ].…”

Section: Epigenetic Modifications and Their Functionsmentioning

confidence: 99%

DNA Glycosylases Define the Outcome of Endogenous Base Modifications

Lirussi

Nilsen

2023

IJMS

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Chemically modified nucleic acid bases are sources of genomic instability and mutations but may also regulate gene expression as epigenetic or epitranscriptomic modifications. Depending on the cellular context, they can have vastly diverse impacts on cells, from mutagenesis or cytotoxicity to changing cell fate by regulating chromatin organisation and gene expression. Identical chemical modifications exerting different functions pose a challenge for the cell’s DNA repair machinery, as it needs to accurately distinguish between epigenetic marks and DNA damage to ensure proper repair and maintenance of (epi)genomic integrity. The specificity and selectivity of the recognition of these modified bases relies on DNA glycosylases, which acts as DNA damage, or more correctly, as modified bases sensors for the base excision repair (BER) pathway. Here, we will illustrate this duality by summarizing the role of uracil-DNA glycosylases, with particular attention to SMUG1, in the regulation of the epigenetic landscape as active regulators of gene expression and chromatin remodelling. We will also describe how epigenetic marks, with a special focus on 5-hydroxymethyluracil, can affect the damage susceptibility of nucleic acids and conversely how DNA damage can induce changes in the epigenetic landscape by altering the pattern of DNA methylation and chromatin structure.

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Section: Epigenetic Modifications and Their Functionsmentioning

confidence: 99%

DNA Glycosylases Define the Outcome of Endogenous Base Modifications

Lirussi

Nilsen

2023

IJMS

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“…The intersection between the cellular RNA milieu and BER is an area of acute interest, although many more questions than answers remain at present [173][174][175]. The only group of DNA glycosylases in which RNA-binding domains are identified is composed of DME-like plant epigenetic 5-methylcytosine-DNA glycosylases (Figure 6, see also Section 3) [92,176,177].…”

Section: Rna-binding Elementsmentioning

confidence: 99%

Noncatalytic Domains in DNA Glycosylases

Torgasheva

Diatlova

Grin

et al. 2022

IJMS

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Many proteins consist of two or more structural domains: separate parts that have a defined structure and function. For example, in enzymes, the catalytic activity is often localized in a core fragment, while other domains or disordered parts of the same protein participate in a number of regulatory processes. This situation is often observed in many DNA glycosylases, the proteins that remove damaged nucleobases thus initiating base excision DNA repair. This review covers the present knowledge about the functions and evolution of such noncatalytic parts in DNA glycosylases, mostly concerned with the human enzymes but also considering some unique members of this group coming from plants and prokaryotes.

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“…SMUG1 is a backup for UNG2 in genomic uracil removal and the main enzyme for in vivo removal of 5-hydroxymethyl uracil (5hmU) in DNA [10]. Importantly, it also has a role in RNA quality control, as reviewed [11]. OGG1 binds to the oxidation product 8-oxoguanine (8-oxoG) in gene promoters and recruits transcription factor NF-κB to promoters [12].…”

Section: Dna Glycosylases-more Than Initiators Of Base Excision Repair (Ber)mentioning

confidence: 99%

Genomic Uracil and Aberrant Profile of Demethylation Intermediates in Epigenetics and Hematologic Malignancies

Oliński

Slupphaug

Foksiński

et al. 2021

IJMS

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DNA of all living cells undergoes continuous structural and chemical alterations resulting from fundamental cellular metabolic processes and reactivity of normal cellular metabolites and constituents. Examples include enzymatically oxidized bases, aberrantly methylated bases, and deaminated bases, the latter largely uracil from deaminated cytosine. In addition, the non-canonical DNA base uracil may result from misincorporated dUMP. Furthermore, uracil generated by deamination of cytosine in DNA is not always damage as it is also an intermediate in normal somatic hypermutation (SHM) and class shift recombination (CSR) at the Ig locus of B-cells in adaptive immunity. Many of the modifications alter base-pairing properties and may thus cause replicative and transcriptional mutagenesis. The best known and most studied epigenetic mark in DNA is 5-methylcytosine (5mC), generated by a methyltransferase that uses SAM as methyl donor, usually in CpG contexts. Oxidation products of 5mC are now thought to be intermediates in active demethylation as well as epigenetic marks in their own rights. The aim of this review is to describe the endogenous processes that surround the generation and removal of the most common types of DNA nucleobase modifications, namely, uracil and certain epigenetic modifications, together with their role in the development of hematological malignances. We also discuss what dictates whether the presence of an altered nucleobase is defined as damage or a natural modification.

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RNA Metabolism Guided by RNA Modifications: The Role of SMUG1 in rRNA Quality Control

Cited by 8 publications

References 178 publications

DNA Glycosylases Define the Outcome of Endogenous Base Modifications

DNA Glycosylases Define the Outcome of Endogenous Base Modifications

Noncatalytic Domains in DNA Glycosylases

Genomic Uracil and Aberrant Profile of Demethylation Intermediates in Epigenetics and Hematologic Malignancies

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