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Existence of Diverse Modifications in Small‐RNA Species Composed of 16–28 Nucleotides
Author(s) -
Lan MengDan,
Xiong Jun,
You XueJiao,
Weng XiaoCheng,
Zhou Xiang,
Yuan BiFeng,
Feng YuQi
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201801640
Subject(s) - rna , small nucleolar rna , transfer rna , small rna , ribosomal rna , biology , rna methylation , rna silencing , methylation , nucleic acid , biochemistry , small nuclear rna , non coding rna , messenger rna , inosine , ribosome , nucleotide , methyltransferase , enzyme , rna interference , gene
RNA contains diverse modifications that exert an important influence in a variety of cellular processes. So far, more than 150 modifications have been identified in various RNA species, mainly in ribosomal RNA (rRNA), transfer RNA (tRNA), and messenger RNA (mRNA). In contrast to rRNA, tRNA, and mRNA, the known modifications in small RNA species have been primarily limited to 2′‐ O ‐ribose methylation in plants and inosine in mammals. The methylation of small RNAs in mammals is still unclear. Current methods widely used in the characterization of small RNAs are mainly based on the strategy of nucleic acid hybridization and sequencing, which cannot characterize modifications in small RNAs. Herein, we have systematically investigated modifications in small RNAs composed of 16–28 nucleotides (nt) by establishing an effective isolation and neutral enzymatic digestion of small RNAs in combination with liquid chromatography/electrospray ionization tandem mass spectrometry (LC‐ESI‐MS/MS). This method allowed us to simultaneously detect 57 different types of nucleoside modification. By using this approach, we revealed 24 modifications in small RNAs comprising 16–28 nt from human cells. In addition, we found that the obesity‐associated protein (FTO) may demethylate N 6 ‐methyladenosine (m 6 A) and N 6 ,2′‐ O ‐dimethyladenosine (m 6 Am) in small RNAs of 16–28 nt. Our study demonstrates the existence of diverse modifications in small RNAs composed of 16–28 nt, which may promote in‐depth understanding of the regulatory roles of noncoding RNAs.