title: A variety of dicer substrates in human and C. elegans.
abstract: The endoribonuclease Dicer is known for its central role in the biogenesis of eukaryotic small RNAs/microRNAs. Despite its importance, Dicer target transcripts have not been directly mapped. Here, we apply biochemical methods to human cells and C. elegans and identify thousands of Dicer-binding sites. We find known and hundreds of additional miRNAs with high sensitivity and specificity. We also report structural RNAs, promoter RNAs, and mitochondrial transcripts as Dicer targets. Interestingly, most Dicer-binding sites reside on mRNAs/lncRNAs and are not significantly processed into small RNAs. These passive sites typically harbor small, Dicer-bound hairpins within intact transcripts and generally stabilize target expression. We show that passive sites can sequester Dicer and reduce microRNA expression. mRNAs with passive sites were in human and worm significantly associated with processing-body/granule function. Together, we provide the first transcriptome-wide map of Dicer targets and suggest conserved binding modes and functions outside of the miRNA pathway.
authors.affiliation: Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Rybak-Wolf
authors.affiliation: Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Marvin
authors.initials: M
authors.lastname: Jens
authors.affiliation: Laboratory for RNA Biology and Posttranscriptional Regulation, Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Murakawa
authors.affiliation: Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Margareta
authors.initials: M
authors.lastname: Herzog
authors.affiliation: Laboratory for RNA Biology and Posttranscriptional Regulation, Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany. Electronic address: markus.landthaler@mdc-berlin.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Landthaler
authors.affiliation: Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany. Electronic address: rajewsky@mdc-berlin.de.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Rajewsky
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D010777:Photochemistry; D012313:RNA / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000077278:RNA, Mitochondrial; D016601:RNA-Binding Proteins / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism*; D024363:Transcription Initiation Site; D059467:Transcriptome
chemical_list: D029742:Caenorhabditis elegans Proteins; C474043:DGCR8 protein, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D000077278:RNA, Mitochondrial; D016601:RNA-Binding Proteins; D012313:RNA; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases