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Review
. 2020 Jul 22;9(8):1758.
doi: 10.3390/cells9081758.

The RNA Methyltransferase NSUN2 and Its Potential Roles in Cancer

Anitha Chellamuthu  1 , Steven G Gray  1   2
Affiliations
Review

The RNA Methyltransferase NSUN2 and Its Potential Roles in Cancer

Anitha Chellamuthu et al. Cells. .

Abstract

5-methylcytosine is often associated as an epigenetic modifier in DNA. However, it is also found increasingly in a plethora of RNA species, predominantly transfer RNAs, but increasingly found in cytoplasmic and mitochondrial ribosomal RNAs, enhancer RNAs, and a number of long noncoding RNAs. Moreover, this modification can also be found in messenger RNAs and has led to an increasing appreciation that RNA methylation can functionally regulate gene expression and cellular activities. In mammalian cells, the addition of m5C to RNA cytosines is carried out by enzymes of the NOL1/NOP2/SUN domain (NSUN) family as well as the DNA methyltransferase homologue DNMT2. In this regard, NSUN2 is a critical RNA methyltransferase for adding m5C to mRNA. In this review, using non-small cell lung cancer and other cancers as primary examples, we discuss the recent developments in the known functions of this RNA methyltransferase and its potential critical role in cancer.

Keywords: 5-methylcytosine; RNA modification; cancer; epi-transcriptome; mRNA; miRNA.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Phylogenetic analysis of RNA methyltransferases (RNMTs): Analysis was conducted using MEGA-X [29]. The sequences of 58 RNMTs were obtained from the ChromoHub database [30] and aligned, and an evolutionary phylogenetic tree was inferred by using the maximum likelihood method and Jones, Taylor & Thornton (JTT) matrix-based model [31], using default parameters. Members of the m5C RNMTs are highlighted in blue.
Figure 2
Figure 2
Pan-cancer expression of NSUN2 (normal vs. tumor) as assessed using UALCAN [94]. Altered expression of NSUN2 can be seen across many cancers.
Figure 3
Figure 3
cBioportal analysis of The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets.
Figure 4
Figure 4
Meta-analysis of NSUN2 for changes in gene expression and survival: All available datasets on Lung Cancer Explorer [114] were assessed by meta-analysis for (A) associations between gene expression of tumor vs. normal and (B) survival using the default settings in the online server.
Figure 5
Figure 5
NSUN2 protein is overexpressed in LUAD samples: The expression of the NSUN2 protein was examined in the Clinical Proteomic Tumor Analysis Consortium (CPTAC) Confirmatory/Discovery dataset for LUAD using UALCAN [94]. Significant overexpression of NSUN2 protein was observed in tumors compared to normal tissues.
Figure 6
Figure 6
NSUN2 has a potential prognostic value in lung cancer. The potential prognostic value of NSUN2 mRNA expression was evaluated using KM-Plot [115]. Patients were split using median expression, and survival was assessed using the default parameters. Analyses were conducted based on (A) all histologies, (B) LUAD, and (C) LUSC.
See this image and copyright information in PMC

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