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Journal Article

Microprocessor activity controls differential miRNA biogenesis In Vivo

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons144853

Conrad,  Thomas
Long non-coding RNA (Ulf Andersson Ørom), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50424

Marsico,  Annalisa
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons144855

Gehre,  Maja
Long non-coding RNA (Ulf Andersson Ørom), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons73949

Ørom,  Ulf Andersson
Long non-coding RNA (Ulf Andersson Ørom), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Conrad, T., Marsico, A., Gehre, M., & Ørom, U. A. (2014). Microprocessor activity controls differential miRNA biogenesis In Vivo. Cell Reports, 9(2), 542-554. doi:10.1016/j.celrep.2014.09.007.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0025-0BA5-B
Abstract
In miRNA biogenesis, pri-miRNA transcripts are converted into pre-miRNA hairpins. The in vivo properties of this process remain enigmatic. Here, we determine in vivo transcriptome-wide pri-miRNA processing using next-generation sequencing of chromatin-associated pri-miRNAs. We identify a distinctive Microprocessor signature in the transcriptome profile from which efficiency of the endogenous processing event can be accurately quantified. This analysis reveals differential susceptibility to Microprocessor cleavage as a key regulatory step in miRNA biogenesis. Processing is highly variable among pri-miRNAs and a better predictor of miRNA abundance than primary transcription itself. Processing is also largely stable across three cell lines, suggesting a major contribution of sequence determinants. On the basis of differential processing efficiencies, we define functionality for short sequence features adjacent to the pre-miRNA hairpin. In conclusion, we identify Microprocessor as the main hub for diversified miRNA output and suggest a role for uncoupling miRNA biogenesis from host gene expression.