2015
DOI: 10.18632/aging.100860
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Abstract: A rise in the levels of the cyclin-dependent kinase (CDK) inhibitor p27KIP1 is important for the growth arrest of senescent cells, but the mechanisms responsible for this increase are poorly understood. Here, we show that the tRNA methyltransferase NSun2 represses the expression of p27 in replicative senescence. NSun2 methylated the 5′-untranslated region (UTR) of p27 mRNA at cytosine C64 in vitro and in cells, thereby repressing the translation of p27. During replicative senescence, increased p27 protein leve… Show more

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Cited by 69 publications
(87 citation statements)
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References 41 publications
(57 reference statements)
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“…All plasmids were transfected using lipofectamine 2000 (Invitrogen) and cells were collected 48–72 h after transfection for further analysis. SA‐β‐galactosidase staining was performed as described previously [Tang et al, ; Cai et al, ].…”
Section: Methodsmentioning
confidence: 99%
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“…All plasmids were transfected using lipofectamine 2000 (Invitrogen) and cells were collected 48–72 h after transfection for further analysis. SA‐β‐galactosidase staining was performed as described previously [Tang et al, ; Cai et al, ].…”
Section: Methodsmentioning
confidence: 99%
“…The p21 3′UTR10 mutants (3′UTRCm [bearing C2079G], 3′UTR10m1 [bearing A1986U], 3′UTR10m2 [bearing A2037U], 3′UTR10m3 [bearing A2044U], 3′UTR10m4 [bearing A2061U], 3′UTR10m5 [bearing A2044U and A2061U] were prepared by overlapping PCR). The p27 5′UTR and SHC 5′UTR fragments were described previously [Tang et al, ; Cai et al, ].…”
Section: Methodsmentioning
confidence: 99%
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“…Expression of the m 5 C writer NOP2/Sun RNA methyltransferase family member 2 (NSUN2) is tightly regulated during the cell cycle and its overexpression delays replicative senescence through methylation of Cyclin-dependent kinase 1 (CDK1) and the CDK inhibitor 1B (p27 KIP1 ) transcripts. Deposition of m 5 C in the CDK1 3′UTR enhances its translation, while m 5 C in the 5′UTR of p27 KIP1 represses its translation, resulting in increased cellular proliferation 56, 57 . Deposition of hm 5 C by methylcytosine dioxygenases 58 in mRNA correlates with higher association with polyribosomes in Drosophila melanogaster 59 .…”
Section: Rna Modification: the Epitranscriptomementioning
confidence: 99%
“…Given the relevance of cellular senescence to mammalian aging, we initiated a systemic investigation as to whether RNA modification regulates RNA abundance during human aging. Specifically, we focused on the m6A RNA modification because it is the most abundant internal modification observed in eukaryotic mRNA, which can affect mRNA splicing and nuclear export; in the cytoplasm, m6A mRNAs are recognized by the RNA‐binding protein (RBP) that will mobilize them to processing (P) bodies, where mRNA stability and translation are modulated (Fu, Dominissini, Rechavi & He, 2014; Licht & Jantsch, 2016; Tang et al., 2015). …”
Section: Introductionmentioning
confidence: 99%