ZFIN ID: ZDB-PUB-151218-14
Transcriptional, post-transcriptional and chromatin-associated regulation of pri-miRNAs, pre-miRNAs and moRNAs
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.
Date: 2016
Source: Nucleic acids research   44(7): 3070-81 (Journal)
Registered Authors: Bally-Cuif, Laure, Coolen, Marion, Cussigh, Delphine, Hadzhiev, Yavor, Müller, Ferenc
Keywords: none
MeSH Terms:
  • Animals
  • Chromatin/metabolism
  • Embryonic Development/genetics
  • Gene Expression Regulation*
  • Histones/metabolism
  • MicroRNAs/genetics*
  • MicroRNAs/metabolism
  • Promoter Regions, Genetic
  • RNA Polymerase II/analysis
  • RNA Precursors/genetics*
  • RNA Precursors/metabolism
  • RNA Processing, Post-Transcriptional*
  • RNA, Small Untranslated/genetics*
  • RNA, Small Untranslated/metabolism
  • Ribonuclease III/metabolism
  • Transcription Initiation Site
  • Transcription, Genetic*
  • Zebrafish/embryology
  • Zebrafish/genetics
PubMed: 26673698 Full text @ Nucleic Acids Res.
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.