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Nucleic Acids Res. 2016 Feb 29;44(4):1525-40. doi: 10.1093/nar/gkw039. Epub 2016 Jan 26.

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

Author information

1
Telethon Institute of Genetics and Medicine, via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, via Luigi De Crecchio 7, 80138 Naples (NA), Italy.
2
Telethon Institute of Genetics and Medicine, via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy.
3
Eye Bank of Venice, Padiglione Rama, via Paccagnella 11, 30174 Zelarino (VE), Italy.
4
Telethon Institute of Genetics and Medicine, via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy Department of Chemical, Materials and Production Engineering, University of Naples 'Federico II', via Claudio 21, 80125 Naples (NA), Italy dibernardo@tigem.it.
5
Telethon Institute of Genetics and Medicine, via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, via Luigi De Crecchio 7, 80138 Naples (NA), Italy banfi@tigem.it.

Abstract

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.

PMID:
26819412
PMCID:
PMC4770244
DOI:
10.1093/nar/gkw039
[Indexed for MEDLINE]
Free PMC Article

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