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Cited by 35MicroRNA in disease regulationGenomics and Chromatin DynamicsPlant Molecular Biology Research

Transcriptional, post-transcriptional and chromatin-associated regulation of pri-miRNAs, pre-miRNAs and moRNAs

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Nepal, Chirag, Coolen, Marion, Hadzhiev, Yavor, Cussigh, Delphine, Mydel, Piotr, Steen, Vidar M., Carninci, Piero, Andersen, Jesper B. +3 more·2016·Nucleic Acids Research
DOI 10.1093/nar/gkv1354PMC PMC4838339
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Abstract

MicroRNAs (miRNAs) play a major role in the post-transcriptional regulation of target genes, especially in development and differentiation. Our understanding about the transcriptional regulation of miRNA genes is limited by inadequate annotation of primary miRNA (pri-miRNA) transcripts. Here, we used CAGE-seq and RNA-seq to provide genome-wide identification of the pri-miRNA core promoter repertoire and its dynamic usage during zebrafish embryogenesis. We assigned pri-miRNA promoters to 152 precursor-miRNAs (pre-miRNAs), the majority of which were supported by promoter associated post-translational histone modifications (H3K4me3, H2A.Z) and RNA polymerase II (RNAPII) occupancy. We validated seven miR-9 pri-miRNAs by in situ hybridization and showed similar expression patterns as mature miR-9. In addition, processing of an alternative intronic promoter of miR-9-5 was validated by 5' RACE PCR. Developmental profiling revealed a subset of pri-miRNAs that are maternally inherited. Moreover, we show that promoter-associated H3K4me3, H2A.Z and RNAPII marks are not only present at pri-miRNA promoters but are also specifically enriched at pre-miRNAs, suggesting chromatin level regulation of pre-miRNAs. Furthermore, we demonstrated that CAGE-seq also detects 3'-end processing of pre-miRNAs on Drosha cleavage site that correlates with miRNA-offset RNAs (moRNAs) production and provides a new tool for detecting Drosha processing events and predicting pre-miRNA processing by a genome-wide assay.

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Authors
Nepal, C., Coolen, M., Hadzhiev, Y., Cussigh, D., Mydel, P., Steen, V. M., Carninci, P., Andersen, J. B., Bally-Cuif, L., Müller, F., & Lenhard, B.
Affiliations
  • University of Copenhagen (DK)
  • Université Paris-Sud (FR)
  • University of Birmingham (GB)
  • Jagiellonian University (PL)
  • University of Bergen (NO)
  • RIKEN (JP)
  • Hammersmith Hospital (GB)
Corresponding author
  • Nepal, Chirag
  • Müller, Ferenc
  • Lenhard, Boris
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2015-12-15
Volume
44
Issue
7
Pages
3070-3081
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkv1354
PMC
PMC4838339
OpenAlex
W2258781589
Cited by
35
References
4
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 7 · 2018: 3 · 2017: 5 · 2016: 3
FWCI
1.21
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Jagiellonian University Repository (Jagiellonian University) (submittedVersion, cc-by-nc-nd)
  • HAL (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
  • Spiral (Imperial College London) (submittedVersion, other-oa)
Funders
  • European Commission (FP7/2010, 322936, 242048, 306029)
  • Agence Nationale de la Recherche (ANR-12-BSV4-0004)
  • Institut National de la Santé et de la Recherche Médicale
  • Ministry of Education, Culture, Sports, Science and Technology
  • Universitetet i Bergen
  • Norges Forskningsråd
  • Bergens Forskningsstiftelse
  • Novo Nordisk Fonden (NNF15OC0014040)
  • Biotechnology and Biological Sciences Research Council (BB/L010488/1, BB/L00741X/1)
  • RIKEN
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
Keywords
microRNA biogenesis, microRNA precursors, miR-9, zebrafish embryonic development, H3K4me3, H2A.Z, RNA polymerase II occupancy, chromatin regulation, 3' end processing, intronic promoter, post-transcriptional regulation
MeSH terms
Animals, Chromatin, Gene Expression Regulation, Histones, Promoter Regions, Genetic, RNA Polymerase II, RNA Precursors, RNA Processing, Post-Transcriptional, Transcription, Genetic, Zebrafish, Transcription Initiation Site, MicroRNAs, Ribonuclease III, Embryonic Development, RNA, Small Untranslated

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