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Cell Rep. 2014 Oct 23;9(2):542-54. doi: 10.1016/j.celrep.2014.09.007. Epub 2014 Oct 9.

Microprocessor activity controls differential miRNA biogenesis In Vivo.

Author information

1
Otto Warburg Laboratories, Noncoding RNA Research Group, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
2
Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Department of Mathematics and Informatics, Free University of Berlin, 14195 Berlin, Germany.
3
Otto Warburg Laboratories, Noncoding RNA Research Group, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Department of Biochemistry, Free University of Berlin, 14195 Berlin, Germany.
4
Otto Warburg Laboratories, Noncoding RNA Research Group, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany. Electronic address: oerom@molgen.mpg.de.

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.

PMID:
25310978
DOI:
10.1016/j.celrep.2014.09.007
[Indexed for MEDLINE]
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