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Table 1 Molecular mechanisms and cellular function of m5C enzymes

From: 5-methylcytosine RNA methyltransferases and their potential roles in cancer

Regulator

Target RNA(s)

Modification installed

Biological functions

Mechanisms

Refs.

NSUN1/NOP2

28S rRNA

m5C4447

Unknown

Unknown

[12]

 

telomerase RNA component

Unknown

Maintain the proliferation of human tumor cells

Activates and regulates cyclin D1 gene transcription

[16]

 

TAR RNA in HIV-1 virus

Unknown

Inhibit viral transcription and increase its latency

Competes with Tat protein binding to TAR

[17]

NSUN2

mRNA

various

Enhance cellular migration

Promotes the translation and export of ATX mRNA

[9] [72]

   

Regulate cellular senescence and proliferation

Regulates the translation of SHC, CDK1, p21, and p27 mRNAs

[33,34,35,36]

   

Mediate vascular inflammation and allograft arteriosclerosis

Upregulates the expression of ICAM-1 mRNA

[32]

 

nuclear or cytoplasmic tRNA

m5C48/49/50

Regulate cellular response to external stress stimuli

Regulates the stability and cleavage of cytoplasmic tRNAs

[40, 41]

   

Regulate protein synthesis of cells

Promotes stability and translational efficiency of tRNA

[42, 43]

 

mitochondrial tRNA

m5C48/49/50

Unknown

Unknown

[44]

 

vtRNA

various

Regulate epidermal differentiation

Determines vtRNA processing to svRNA

[47, 48]

 

microRNA-125b

m6A9,15

Repress the function of silencing gene expression

Inhibits processing and maturation of microRNA

[45, 46]

 

lncRNA

various

Regulate the progression of cancer

Enhances lncRNA stability

[49, 50]

NSUN3

mt-tRNAMet

m5C34

Promote mitochondrial translation and regulate mitochondrial activity

Enables mt-tRNAMet to recognize AUA and AUG codons

[6, 75, 76]

NSUN4

mt-12S rRNA

m5C911

Regulate mitochondrial protein synthesis

Regulates maturation and assembly of mt-ribosome

[82,83,84,85,86,87,88,89,90,91]

NSUN5

28S rRNA

m5C3782

Regulate global protein synthesis and proliferation of cells

Maintains the structural stability of the tertiary complex rRNA–tRNA–mRNA

[94, 95]

 

Tpm1 mRNA?

Unknown

Maintain the normal morphogenesis of the cardiac outflow tract

Regulates the translation of Tpm1 mRNA

[99]

NSUN6

tRNACys/Thr

m5C72

Unknown

Unknown

[104]

 

mRNA

various

Suppress the development of pancreatic cancer

May enhance expression of CDK10 mRNA

[154]

   

Regulate bone metastasis of breast cancer

Affects the kinase activity of MST1 and activate YAP

[105]

NSUN7

eRNA

Unknown

May regulate cellular metabolism

Enhances the transcription and stability of eRNA

[106]

DNMT2

tRNAAsp

m5C38

Regulate cellular response to external stress stimuli

Regulates tRNA stability and mediates its cleavage

[43, 116,117,118]

   

Regulate cellular differentiation and protein synthesis accuracy

Discriminates near-cognate codons

[119]

 

mRNA?

Unknown

Affect the migration and invasion of HEK293 cells

Unknown

[120]