A-to-I editing in human miRNAs is enriched in seed sequence, influenced by sequence contexts and significantly hypoedited in glioblastoma multiforme

Paul, D; Sinha, AN; Ray, A; Lal, M; Nayak, S; Sharma, A; Mehani, B; Mukherjee, D; Laddha, SV; Suri, A; Sarkar, C; Mukhopadhyay, A

Abstract

Editing in microRNAs, particularly in seed can significantly alter the choice of their target genes. We show that out of 13 different human tissues, different regions of brain showed higher adenosine to inosine (A-to-I) editing in mature miRNAs. These events were enriched in seed sequence (73.33%), which was not observed for cytosine to uracil (17.86%) editing. More than half of the edited miRNAs showed increased stability, 72.7% of which had ΔΔG values less than -6.0 Kcal/mole and for all of them the edited adenosines mis-paired with cytosines on the pre-miRNA structure. A seed-editing event in hsa-miR-411 (with A – C mismatch) lead to increased expression of the mature form compared to the unedited version in cell culture experiments. Further, small RNA sequencing of GBM patient identified significant miRNA hypoediting which correlated with downregulation of ADAR2 both in metadata and qRT-PCR based validation. Twenty-two significant (11 novel) A-to-I hypoediting events were identified in GBM samples. This study highlights the importance of specific sequence and structural requirements of pre-miRNA for editing along with a suggestive crucial role for ADAR2. Enrichment of A-to-I editing in seed sequence highlights this as an important layer for genomic regulation in health and disease, especially in human brain.

• Journal Article Type: Article
• Acceptance Date: Apr 18, 2017
• Online Publication Date: May 26, 2017
• Publication Date: May 26, 2017
• Deposit Date: Apr 24, 2017
• Publicly Available Date: Jun 12, 2017
• Journal: Scientific Reports
• Print ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Volume: 7
• Issue: 2466
• DOI: https://doi.org/10.1038/s41598-017-02397-6
• Publisher URL: http://dx.doi.org/10.1038/s41598-017-02397-6
• Related Public URLs: http://www.nature.com/srep/
• Additional Information: Projects : Genome dynamics in cellular organization, differentiation and enantiostasis