The Processing, Gene Regulation, Biological Functions, and Clinical Relevance of N4-Acetylcytidine on RNA: A Systematic Review

Jin, Gehui; Xu, Mingqing; Zou, Mengsha; Duan, Shiwei

doi:10.1016/j.omtn.2020.01.037

Cited by 134 publications

(108 citation statements)

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“…Specifically, N 6 -methyladenosine plays an important role in mediating the functions of MSCs, including osteogenic differentiation [19]. Recently, ac 4 C was proven to be conserved and extensively distributed on mRNAs, contributing to their transcription and translation [7]. This modification ultimately affects various functions in various cells.…”

Section: Discussionmentioning

confidence: 99%

“…The functions of MSCs are controlled by various kinds of RNA modifications [6]. Recently, N 4 -acetylcytidine (ac 4 C) modification was found to be widely distributed on RNA in human cells [7]. Messenger RNAs (mRNAs) modified by ac 4 C exhibit differences in their stability and degradation rate, therefore affecting the expression of genes and the subsequent functions of cells [8].…”

Section: Introductionmentioning

confidence: 99%

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NAT10 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells by Mediating N4-Acetylcytidine Modification of Gremlin 1

Zhu

Xing

Huang

et al. 2021

Stem Cells International

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Objective. To investigate the function of NAT10 in mesenchymal stem cell (MSC) osteogenic differentiation and study the mechanism by which NAT10 affects MSC osteogenesis by mediating Gremlin 1 N4-acetylcytidine (ac4C) modification. Methods. Osteogenic differentiation of MSCs was induced, and the osteogenic ability was evaluated with alizarin red S (ARS) and alkaline phosphatase (ALP) assays. The NAT10 expression level during MSC osteogenesis was measured by western blot (WB). MSCs were transfected with lentiviruses to inhibit (Sh-NAT10) or overexpress NAT10 (Over-NAT10), and the osteogenic differentiation ability was assessed by ARS, ALP, and osteogenic gene marker assays. β-Catenin, Akt, and Smad signaling pathway component activation levels were assessed, and the expression levels of key Smad signaling pathway molecules were determined by PCR and WB. The Gremlin 1 mRNA ac4C levels were analyzed using RIP-PCR, and the Gremlin 1 mRNA degradation rate was determined. Sh-Gremlin 1 was transfected to further investigate the role of NAT10 and Gremlin 1 in MSC osteogenesis. Results. During MSC osteogenesis, NAT10 expression, ARS staining, and the ALP level gradually increased. Decreasing NAT10 expression inhibited, and increasing NAT10 expression promoted MSC osteogenic differentiation. NAT10 affected the BMP/Smad rather than the Akt and β-Catenin signaling pathway activation by regulating Gremlin 1 expression. The Gremlin 1 mRNA ac4C level was positively regulated by NAT10, which accelerated Gremlin 1 degradation. Sh-Gremlin 1 abolished the promotive effect of NAT10 on MSC osteogenic differentiation. Conclusion. NAT10 positively regulated MSC osteogenic differentiation through accelerating the Gremlin 1 mRNA degradation by increasing its ac4C level. These results may provide new mechanistic insight into MSC osteogenesis and bone metabolism in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

NAT10 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells by Mediating N4-Acetylcytidine Modification of Gremlin 1

Zhu

Xing

Huang

et al. 2021

Stem Cells International

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“…In recent years, N4-acetylcytidine (ac4C) has become a research hotspot and has been paid wide attention. Recent studies have shown extensive ac4C modifications in human and yeast mRNAs [ 40 ]. And ac4C helps to correctly read codons during translation and improves translation efficiency and the stability of mRNA [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

COL3A1 rs1800255 polymorphism is associated with pelvic organ prolapse susceptibility in Caucasian individuals: Evidence from a meta-analysis

Ning

2021

PLoS ONE

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Background The collagen 3 alpha 1 (COL3A1) rs1800255 polymorphism has been reported to be associated with women pelvic organ prolapse (POP) susceptibility, but the results of these previous studies have been contradictory. The objective of current study is to explore whether COL3A1 rs1800255 polymorphism confers risk to POP. Methods Relevant literatures were searched by searching databases including Pubmed, Embase, Google academic, the Cochrane library, China National Knowledge Infrastructure (CNKI). Search time is from database foundation to March 2021. Results A total of seven literatures were enrolled in the present meta-analysis, including 1642 participants. Overall, no significant association was found by any genetic models. In subgroup analysis based on ethnicity, significant associations were demonstrated in Caucasians by allele contrast (A vs. G: OR = 1.34, 95%CI = 1.03–1.74,), homozygote comparison (AA vs. GG: OR = 3.25, 95%CI = 1.39–7.59), and recessive genetic model (AA vs. GG/GA: OR = 3.22, 95%CI = 1.40–7.42). Conclusions The present meta-analysis suggests that the COL3A1 is a candidate gene for POP susceptibility. Caucasian individuals with A allele and AA genotype have a higher risk of POP. The COL3A1 rs1800255 polymorphism may be risk factor for POP in Caucasian population.

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“…Interestingly, ac 4 C has also been described in mRNAs, catalyzed by the same N-acetyltransferase (NAT10)(discussed above). Acetylation of cytidine appears to preferentially occur near the translation initiation codon in mRNA (Arango et al 2018); however, it is unclear if the location of ac 4 C in mammalian cells is guided by snoRNAs (as described in yeast) (Jin et al 2020), or if NAT10 acts in an RNAindependent manner. Whether cytidine acetylation can be reversed and/or if specific RNA binding proteins can recognize this modification is also unknown, although a role for ac 4 C in promoting translation efficiency has been proposed (Arango et al 2018).…”

Section: Connecting Translation To Metabolism: a Case For Tunable Modmentioning

confidence: 99%

From canonical to modified nucleotides: balancing translation and metabolism

Accornero

Ross

Alfonzo

2020

Critical Reviews in Biochemistry and Molecular Biology

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Every type of nucleic acid in cells may undergo some kind of post-replicative or post-transcriptional chemical modification. Recent evidence has highlighted their importance in biology and their chemical complexity. In the following pages, we will describe new discoveries of modifications, with a focus on tRNA and mRNA. We will highlight current challenges and advances in modification detection and we will discuss how changes in nucleotide post-transcriptional modifications may affect cell homeostasis leading to malfunction. Although, RNA modifications prevail in all forms of life, the present review will focus on eukaryotic systems, where the great degree of intracellular compartmentalization provides barriers and filters for the level at which a given RNA is modified and will of course affect its fate and function. Additionally, although we will mention rRNA modification and modifications of the mRNA 5'-CAP structure, this will only be discussed in passing, as many substantive reviews have been written on these subjects. Here we will not spend much time describing all the possible modifications that have been observed; truly a daunting task. For reference, Bujnicki and coworkers have created MODOMICS, a useful repository for all types of modifications and their associated enzymes. Instead we will discuss a few examples, which illustrate our arguments on the connection of modifications, metabolism and ultimately translation. The fact remains, a full understanding of the long reach of nucleic acid modifications in cells requires both a global and targeted study of unprecedented scale, which at the moment may well be limited only by technology.

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The Processing, Gene Regulation, Biological Functions, and Clinical Relevance of N4-Acetylcytidine on RNA: A Systematic Review

Abstract: The content of ac4C in human body fluids changes significantly under disease conditions (Figure 3). Specifically, the ac4C content in the urine of patients with disease is significantly higher than that of healthy people, including gestational diabetes, 25 interstitial cystitis

Cited by 134 publications

References 70 publications

NAT10 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells by Mediating N4-Acetylcytidine Modification of Gremlin 1

NAT10 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells by Mediating N4-Acetylcytidine Modification of Gremlin 1

COL3A1 rs1800255 polymorphism is associated with pelvic organ prolapse susceptibility in Caucasian individuals: Evidence from a meta-analysis

From canonical to modified nucleotides: balancing translation and metabolism

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