Li Sung-Chou, Tsai Kuo-Wang, Pan Hung-Wei, Jeng Yung-Ming, Ho Meng-Ru, Li Wen-Hsiung
Genomics Research Center, Academia Sinica, Taipei, Taiwan.
BMC Syst Biol. 2012;6 Suppl 2(Suppl 2):S14. doi: 10.1186/1752-0509-6-S2-S14. Epub 2012 Dec 12.
The expression of microRNA (miRNA) genes undergoes several maturation steps. Recent studies brought new insights into the maturation process, but also raised debates on the maturation mechanism. To understand the mechanism better, we downloaded small RNA sequence reads from NCBI SRA and quantified the expression profiles of miRNAs in normal and tumor liver tissues.
From these miRNA expression profiles, we studied several issues related to miRNA biogenesis. First of all, the 3' ends of mature miRNAs usually carried modified nucleotides, generated from nucleotide addition or RNA editing. We found that adenine accounted for more than 50% of all miRNA 3' end modification events in all libraries. However, uracil dominated over adenine in several miRNA types. Moreover, the miRNA reads in the HBV-associated libraries have much lower rates of nucleotide modification. These results indicate that miRNA 3' end modifications are miRNA specific and may differ between normal and tumor tissues. Secondly, according to the hydrogen-bonding theory, the expression ratio of 5p arm to 3p arm miRNAs, derived from the same pre-miRNA, should be constant over tissues. However, a comparison of the expression profiles of the 5p arm and 3p arm miRNAs showed that one arm is preferred in the normal liver tissue whereas the other is preferred in the tumor liver tissue. In other words, different liver tissues have their own preferences on selecting either arm to be mature miRNAs.
The results suggest that besides the traditional miRNA biogenesis theory, another mechanism may also participate in the miRNA biogenesis pathways.
微小RNA（miRNA）基因的表达经历多个成熟步骤。近期研究为成熟过程带来了新见解，但也引发了关于成熟机制的争论。为了更好地理解该机制，我们从NCBI SRA下载了小RNA序列读数，并对正常和肿瘤肝脏组织中miRNA的表达谱进行了定量分析。
基于这些miRNA表达谱，我们研究了几个与miRNA生物合成相关的问题。首先，成熟miRNA的3'端通常携带由核苷酸添加或RNA编辑产生的修饰核苷酸。我们发现，在所有文库中，腺嘌呤占所有miRNA 3'端修饰事件的50%以上。然而，在几种miRNA类型中，尿嘧啶的占比超过腺嘌呤。此外，与乙肝病毒相关的文库中的miRNA读数的核苷酸修饰率要低得多。这些结果表明，miRNA 3'端修饰具有miRNA特异性，并且在正常组织和肿瘤组织之间可能存在差异。其次，根据氢键理论，源自同一前体miRNA的5p臂与3p臂miRNA的表达比例在不同组织中应保持恒定。然而，对5p臂和3p臂miRNA表达谱的比较表明：正常肝脏组织中偏好其中一个臂，而肿瘤肝脏组织中则偏好另一个臂。换句话说，不同的肝脏组织在选择成熟miRNA的臂上有各自的偏好。
结果表明，除了传统的miRNA生物合成理论外，另一种机制可能也参与了miRNA生物合成途径。
