导读：一种新技术有助于研究人员找出促进癌症发生的基因信息的精确位置，研究小组使用一种新的绘图技术来揭示RNA中修饰标记所在的位置。细胞内的酶能够修饰RNA，同时留下已知为m5C位点的标记，修饰RNA的一些酶经证实与癌症和干细胞生物特征相关联。理解这些修饰的模式将有助于研究RNA在促进癌症产生中所起的作用。
RNA修饰图谱追踪癌症发生线索
一种新技术有助于研究人员找出促进癌症发生的基因信息的精确位置。相对于DNA而言，人们对RNA知之较少。澳大利亚国立大学约翰-卡廷医学研究学院Thomas Preiss教授领导的一个研究小组使用一种新的绘图技术来揭示RNA中修饰标记所在的位置。
Preiss教授说，“RNA作为一种信使携带基因信息到细胞内蛋白制造的地方。细胞内的酶能够修饰RNA，同时留下已知为m5C位点的标记。”
“修饰RNA的一些酶经证实与癌症和干细胞生物特征相关联。理解这些修饰的模式将有助于癌症研究人员将他们的关注点集中于RNA在促进癌症产生中所起的作用。”
在这项研究中，研究人员首次在RNA上全面地描绘这些修饰，并鉴定出上万个新的修饰位点。他们发现这些位点要比人们之前所认为的更加普遍，而且还呈现有规则分布而不是人们以前认为的随机分布，另外它们存在于基因标记的附近。这项研究发表在《核酸研究》（Nucleic Acids Research）期刊上。
Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA
Jeffrey E. Squires, Hardip R. Patel, Marco Nousch, Tennille Sibbritt, David T. Humphreys, Brian J. Parker, Catherine M. Suter and Thomas Preiss
The modified base 5-methylcytosine (m5C) is well studied in DNA, but investigations of its prevalence in cellular RNA have been largely confined to tRNA and rRNA. In animals, the two m5C methyltransferases NSUN2 and TRDMT1 are known to modify specific tRNAs and have roles in the control of cell growth and differentiation. To map modified cytosine sites across a human transcriptome, we coupled bisulfite conversion of cellular RNA with next-generation sequencing. We confirmed 21 of the 28 previously known m5C sites in human tRNAs and identified 234 novel tRNA candidate sites, mostly in anticipated structural positions. Surprisingly, we discovered 10 275 sites in mRNAs and other non-coding RNAs. We observed that distribution of modified cytosines between RNA types was not random; within mRNAs they were enriched in the untranslated regions and near Argonaute binding regions. We also identified five new sites modified by NSUN2, broadening its known substrate range to another tRNA, the RPPH1 subunit of RNase P and two mRNAs. Our data demonstrates the widespread presence of modified cytosines throughout coding and non-coding sequences in a transcriptome, suggesting a broader role of this modification in the post-transcriptional control of cellular RNA function.
