Imperial College London
Portrait Picture

ProfessorBorisLenhard

Faculty of Medicine, Institute of Clinical Sciences

Professor of Computational Biology
 
 
 
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Contact

 

+44 (0)20 7594 0911b.lenhard Website

 
 
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Assistant

 

Mr Alastair Douglas Ivor Williams +44 (0)20 3313 4318

 
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Location

 

6.12CLMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Nepal:2015:nar/gkv1354,
author = {Nepal, C and Coolen, M and Hadzhiev, Y and Cussigh, D and Mydel, P and Steen, VM and Carninci, P and Andersen, JB and Bally-Cuif, L and Müller, F and Lenhard, B},
doi = {nar/gkv1354},
journal = {Nucleic Acids Research},
pages = {3070--3081},
title = {Transcriptional, post-transcriptional and chromatin-associated regulation of pri-miRNAs, pre-miRNAs and moRNAs},
url = {http://dx.doi.org/10.1093/nar/gkv1354},
volume = {44},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Nepal,C
AU  - Coolen,M
AU  - Hadzhiev,Y
AU  - Cussigh,D
AU  - Mydel,P
AU  - Steen,VM
AU  - Carninci,P
AU  - Andersen,JB
AU  - Bally-Cuif,L
AU  - Müller,F
AU  - Lenhard,B
DO  - nar/gkv1354
EP  - 3081
PY  - 2015///
SN  - 1362-4962
SP  - 3070
TI  - Transcriptional, post-transcriptional and chromatin-associated regulation of pri-miRNAs, pre-miRNAs and moRNAs
T2  - Nucleic Acids Research
UR  - http://dx.doi.org/10.1093/nar/gkv1354
UR  - http://hdl.handle.net/10044/1/32994
VL  - 44
ER  -
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