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

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 (...

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Autores principales:	Deepanjan Paul, Ashis Narayan Sinha, Arjun Ray, Megha Lal, Subhashree Nayak, Anchal Sharma, Bharati Mehani, Debasish Mukherjee, Saurabh V. Laddha, Ashish Suri, Chitra Sarkar, Arijit Mukhopadhyay
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/12befe50b2ad46caad4d487ba67f6726
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spelling	oai:doaj.org-article:12befe50b2ad46caad4d487ba67f67262021-12-02T16:08:24ZA-to-I editing in human miRNAs is enriched in seed sequence, influenced by sequence contexts and significantly hypoedited in glioblastoma multiforme10.1038/s41598-017-02397-62045-2322https://doaj.org/article/12befe50b2ad46caad4d487ba67f67262017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02397-6https://doaj.org/toc/2045-2322Abstract 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 patients 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.Deepanjan PaulAshis Narayan SinhaArjun RayMegha LalSubhashree NayakAnchal SharmaBharati MehaniDebasish MukherjeeSaurabh V. LaddhaAshish SuriChitra SarkarArijit MukhopadhyayNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Deepanjan Paul Ashis Narayan Sinha Arjun Ray Megha Lal Subhashree Nayak Anchal Sharma Bharati Mehani Debasish Mukherjee Saurabh V. Laddha Ashish Suri Chitra Sarkar Arijit Mukhopadhyay A-to-I editing in human miRNAs is enriched in seed sequence, influenced by sequence contexts and significantly hypoedited in glioblastoma multiforme
description	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 patients 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.
format	article
author	Deepanjan Paul Ashis Narayan Sinha Arjun Ray Megha Lal Subhashree Nayak Anchal Sharma Bharati Mehani Debasish Mukherjee Saurabh V. Laddha Ashish Suri Chitra Sarkar Arijit Mukhopadhyay
author_facet	Deepanjan Paul Ashis Narayan Sinha Arjun Ray Megha Lal Subhashree Nayak Anchal Sharma Bharati Mehani Debasish Mukherjee Saurabh V. Laddha Ashish Suri Chitra Sarkar Arijit Mukhopadhyay
author_sort	Deepanjan Paul
title	A-to-I editing in human miRNAs is enriched in seed sequence, influenced by sequence contexts and significantly hypoedited in glioblastoma multiforme
title_short	A-to-I editing in human miRNAs is enriched in seed sequence, influenced by sequence contexts and significantly hypoedited in glioblastoma multiforme
title_full	A-to-I editing in human miRNAs is enriched in seed sequence, influenced by sequence contexts and significantly hypoedited in glioblastoma multiforme
title_fullStr	A-to-I editing in human miRNAs is enriched in seed sequence, influenced by sequence contexts and significantly hypoedited in glioblastoma multiforme
title_full_unstemmed	A-to-I editing in human miRNAs is enriched in seed sequence, influenced by sequence contexts and significantly hypoedited in glioblastoma multiforme
title_sort	a-to-i editing in human mirnas is enriched in seed sequence, influenced by sequence contexts and significantly hypoedited in glioblastoma multiforme
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/12befe50b2ad46caad4d487ba67f6726
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A-to-I editing in human miRNAs is enriched in seed sequence, influenced by sequence contexts and significantly hypoedited in glioblastoma multiforme

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