High-resolution analysis of the human retina miRNome reveals isomiR variations and novel microRNAs.
High-resolution analysis of the human retina miRNome reveals isomiR variations and novel microRNAs.
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DOI：
10.1093/nar/gkw039
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发表时间：
2016-02-29
影响因子：
14.9
通讯作者：
Banfi S
中科院分区：
文献类型：
--
作者：
Karali M;Persico M;Mutarelli M;Carissimo A;Pizzo M;Singh Marwah V;Ambrosio C;Pinelli M;Carrella D;Ferrari S;Ponzin D;Nigro V;di Bernardo D;Banfi S
MicroRNAs在视网膜发育和功能中起着重要作用。为了描述人类视网膜的miRNome，我们对16个个体进行了深入的测序分析。我们建立了视网膜表达的miRNAs的目录，测定了它们的相对丰度，发现少量的miRNAs几乎占视网膜miRNome的90%。我们发现了3000多个miRNA变体(异构体)，涵盖了广泛的序列变异，其中包括预计会对miRNA作用产生影响的种子修饰。我们证明了富含视网膜的miR-124-3P的种子修饰异构体R相对于相应的规范形式具有不同的靶向特性。此外，我们鉴定了51个假定的新颖的、视网膜特异的miRNAs，并在实验中验证了其中9个的表达。最后，对人类视网膜色素上皮(RPE)/脉络膜的平行分析，这两种已知对视网膜动态平衡至关重要的组织，与视网膜相比，产生了明显不同的miRNA浓缩模式。生成的数据可通过临时数据库访问。这项研究首次揭示了人类视网膜miRNome在核苷酸分辨率上的复杂性，并构成了评估miRNAs对人类视网膜病理生理学的贡献的独特资源。
MicroRNAs play a fundamental role in retinal development and function. To characterise the miRNome of the human retina, we carried out deep sequencing analysis on sixteen individuals. We established the catalogue of retina-expressed miRNAs, determined their relative abundance and found that a small number of miRNAs accounts for almost 90% of the retina miRNome. We discovered more than 3000 miRNA variants (isomiRs), encompassing a wide range of sequence variations, which include seed modifications that are predicted to have an impact on miRNA action. We demonstrated that a seed-modifying isomiR of the retina-enriched miR-124-3p was endowed with different targeting properties with respect to the corresponding canonical form. Moreover, we identified 51 putative novel, retina-specific miRNAs and experimentally validated the expression for nine of them. Finally, a parallel analysis of the human Retinal Pigment Epithelium (RPE)/choroid, two tissues that are known to be crucial for retina homeostasis, yielded notably distinct miRNA enrichment patterns compared to the retina. The generated data are accessible through an ad hoc database. This study is the first to reveal the complexity of the human retina miRNome at nucleotide resolution and constitutes a unique resource to assess the contribution of miRNAs to the pathophysiology of the human retina.