Publications

• NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs.

  Hussain S., Sajini A.A., Blanco S., Dietmann S., Lombard P., Sugimoto Y., Paramor M., Gleeson J.G., Odom D.T., Ule J., Frye M.

  Autosomal-recessive loss of the NSUN2 gene has been identified as a causative link to intellectual disability disorders in humans. NSun2 is an RNA methyltransferase modifying cytosine-5 in transfer RNAs (tRNAs), yet the identification of cytosine methylation in other RNA species has been hampered ... >> More

  Autosomal-recessive loss of the NSUN2 gene has been identified as a causative link to intellectual disability disorders in humans. NSun2 is an RNA methyltransferase modifying cytosine-5 in transfer RNAs (tRNAs), yet the identification of cytosine methylation in other RNA species has been hampered by the lack of sensitive and reliable molecular techniques. Here, we describe miCLIP as an additional approach for identifying RNA methylation sites in transcriptomes. miCLIP is a customized version of the individual-nucleotide-resolution crosslinking and immunoprecipitation (iCLIP) method. We confirm site-specific methylation in tRNAs and additional messenger and noncoding RNAs (ncRNAs). Among these, vault ncRNAs contained six NSun2-methylated cytosines, three of which were confirmed by RNA bisulfite sequencing. Using patient cells lacking the NSun2 protein, we further show that loss of cytosine-5 methylation in vault RNAs causes aberrant processing into Argonaute-associated small RNA fragments that can function as microRNAs. Thus, impaired processing of vault ncRNA may contribute to the etiology of NSun2-deficiency human disorders. << Less

  Cell Rep. 4:255-261(2013) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.

• 5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs.

  Chen X., Li A., Sun B.F., Yang Y., Han Y.N., Yuan X., Chen R.X., Wei W.S., Liu Y., Gao C.C., Chen Y.S., Zhang M., Ma X.D., Liu Z.W., Luo J.H., Lyu C., Wang H.L., Ma J., Zhao Y.L., Zhou F.J., Huang Y., Xie D., Yang Y.G.

  Although 5-methylcytosine (m⁵C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA m⁵C modifications in human urothel ... >> More

  Although 5-methylcytosine (m⁵C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA m⁵C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m⁵C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m⁵C 'reader' recognizing m⁵C-modified mRNAs through the indole ring of W65 in its cold-shock domain. YBX1 maintains the stability of its target mRNA by recruiting ELAVL1. Moreover, NSUN2 and YBX1 are demonstrated to drive UCB pathogenesis by targeting the m⁵C methylation site in the HDGF 3' untranslated region. Clinically, a high coexpression of NUSN2, YBX1 and HDGF predicts the poorest survival. Our findings reveal an unprecedented mechanism of RNA m⁵C-regulated oncogene activation, providing a potential therapeutic strategy for UCB. << Less

  Nat. Cell Biol. 21:978-990(2019) [PubMed] [EuropePMC]