A genome-wide screen for non-template nucleotides and isomiR repertoires in miRNAs indicates dynamic and versatile microRNAome
A genome-wide screen for non-template nucleotides and isomiR repertoires in miRNAs indicates dynamic and versatile microRNAome
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对 miRNA 中非模板核苷酸和 isomiR 库的全基因组筛选表明了动态和多功能的 microRNAome
DOI：
10.1007/s11033-014-3548-0
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发表时间：
2014-10-01
影响因子：
2.8
通讯作者：
Chen, Feng
中科院分区：
文献类型：
--
作者：
Guo, Li;Zhao, Yang;Chen, Feng
miRNA变体（称为isomiR）已被报道为可能影响miRNA稳定性或靶标选择的潜在功能分子。本研究的目的是全面调查和表征miRNAs中的非模板核苷酸（NTNs）和isomiR库。50%以上的NTN位于3′端（也称为3′加成），其次是5′端和5′和3′端的邻近位置。NTN和isomiR库在同源或成簇的miRNAs之间可能检测到相似的分布。基于典型分析，miRNA可能稳定表达，但其isomiRs可能强烈上调或下调。具有新种子序列的isomiRs主要来源于5′ isomiRs中的“种子移位”事件、5′端的NTN或种子序列中的NTN。来自同一个miRNA位点或同源miRNA位点的IsomiR可能具有相同的种子序列，但它们可能具有不同的富集水平和3′端。有趣的是，在种子区通过NTN具有新种子序列的isomiR物种总是稳定表达。这些新的种子序列可能通过驱动潜在的新靶mRNA而导致新的功能作用。整合预测的靶mRNA和进一步的微阵列验证表明，这些isomiRs具有多功能的生物学作用。总的来说，多种isomiR产物和miRNA成熟过程提供了在调控网络中发挥多种作用的机会，这进一步丰富和复杂化了生物过程的调控。
miRNA variants (termed isomiRs) have been reported as potential functional molecules that may affect miRNA stability or target selection. The aims of the present study were to comprehensively survey and characterize non-template nucleotides (NTNs) and isomiR repertoires in miRNAs. Over 50 % of the NTNs were located in the 3′ ends (also termed 3′ additions), followed by the 5′ ends and adjacent positions to 5′ and 3′ ends. The similar distributions of NTNs and isomiR repertoires might be detected between homologous or clustered miRNAs. miRNA might be stably expressed based on the typical analysis, but its isomiRs might be strongly up- or down-regulated. IsomiRs with novel seed sequences were mainly derived from “seed shifting” events in 5′ isomiRs, NTNs in 5′ ends or in seed sequences. IsomiRs from a miRNA locus or homologous miRNA loci maybe have the same seed sequences, but they would have various enrichment levels and 3′ ends. Interestingly, isomiR species with novel seed sequences via NTNs in the seed region were always stably expressed. These novel seed sequences could lead to novel functional roles through driving the potential novel target mRNAs. Integrated predicted target mRNAs and further microarray validation showed that these isomiRs have versatile biological roles. Collectively, multiple isomiR products and miRNA maturation processes provide opportunities to perform versatile roles in the regulatory network, which further enriches and complicates the regulation of biological processes.