The RNA Methyltransferase NSUN2 and Its Potential Roles in Cancer

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.

Bioinformatics analysis of DNMT1 expression and its role in head and neck squamous cell carcinoma prognosis

“…DNMTs are involved in initiation of mammalian chromatin remodeling and gene expression regulation in diverse physiological and pathophysiological processes 23 , 24 . m5C functions as an important epigenetic modifier in DNA and RNA with transcriptional expression 25 . m5C plays vital roles in HNSCC carcinogenesis and tumor progression 22 .…”

Methylation multiplicity and its clinical values in cancer

“…The m5C methyltransferase NSUN2 is over-expressed in multiple types of tumours such as breast and colorectal malignancies (Ref. 113 ). NSUN2 protein expression was found to be upregulated in 34% breast tumours through immunohistochemical analysis of tissue microarrays (Ref.…”

RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases

“…RCMTs are known to play a wide variety of roles, notably ribosomal assembly, transcription regulation, mRNA nuclear export and tRNA cleavage and charging [ 55 ]. NSUN2 is known to be responsible for the majority of m 5 C in mRNA [ 56 , 57 ]. NSUN6 has been shown to be implicated in the formation of m 5 C in mRNA [ 58 ].…”

“…In eukaryotes, RNA m 5 C is catalyzed by RCMTs, including NOL1/NOP2/SUN domain (NSUN) family enzymes and DNMT2 ( Figure 2 B). NSUN2 is responsible for catalyzing the majority of m 5 C in mRNAs and non-coding RNAs [ 57 , 228 , 229 ]. Our study demonstrated a marked increase in NOP2/NSUN1 and NSUN2-mediated m 5 C in drug (5-azacitidine) resistant myeloid leukemia cells [ 127 ].…”

“…NSUN2 is responsible for the majority of mRNA:m 5 C in mammalian cells and is upregulated in various cancer types [ 57 , 389 ]. NSUN2 was found to be a downstream regulator of MYC and promotes cancer cell proliferation by RNAPIII methylation [ 390 ].…”