High-resolution analysis of the human retina miRNome reveals isomiR variations and novel microRNAs

被引:96
|
作者
Karali, Marianthi [1 ,2 ]
Persico, Maria [1 ]
Mutarelli, Margherita [1 ]
Carissimo, Annamaria [1 ]
Pizzo, Mariateresa [1 ]
Marwah, Veer Singh [1 ]
Ambrosio, Concetta [1 ]
Pinelli, Michele [1 ]
Carrella, Diego [1 ]
Ferrari, Stefano [3 ]
Ponzin, Diego [3 ]
Nigro, Vincenzo [1 ,2 ]
di Bernardo, Diego [1 ,4 ]
Banfi, Sandro [1 ,2 ]
机构
[1] Telethon Inst Genet & Med, Via Campi Flegrei 34, I-80078 Pozzuoli, NA, Italy
[2] Univ Naples 2, Dept Biochem Biophys & Gen Pathol, Via Luigi De Crecchio 7, I-80138 Naples, NA, Italy
[3] Eye Bank Venice, Padigl Rama,Via Paccagnella 11, I-30174 Zelarino, VE, Italy
[4] Univ Naples Federico II, Dept Chem Mat & Prod Engn, Via Claudio 21, I-80125 Naples, NA, Italy
关键词
MOUSE RETINA; ANIMAL DEVELOPMENT; SMALL RNAS; EXPRESSION; DIFFERENTIATION; CLUSTER; IMPACT; GENES; INACTIVATION; DEGENERATION;
D O I
10.1093/nar/gkw039
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1525 / 1540
页数:16
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