Details
- Autor(en) / Beteiligte
- Titel
- A Compendium of RNA-Binding Proteins that Regulate MicroRNA Biogenesis
- Ist Teil von
- Molecular cell, 2017-04, Vol.66 (2), p.270-284.e13
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- Elsevier ScienceDirect Journals Complete
- Beschreibungen/Notizen
- During microRNA (miRNA) biogenesis, two endonucleolytic reactions convert stem-loop-structured precursors into mature miRNAs. These processing steps can be posttranscriptionally regulated by RNA-binding proteins (RBPs). Here, we have used a proteomics-based pull-down approach to map and characterize the interactome of a multitude of pre-miRNAs. We identify ∼180 RBPs that interact specifically with distinct pre-miRNAs. For functional validation, we combined RNAi and CRISPR/Cas-mediated knockout experiments to analyze RBP-dependent changes in miRNA levels. Indeed, a large number of the investigated candidates, including splicing factors and other mRNA processing proteins, have effects on miRNA processing. As an example, we show that TRIM71/LIN41 is a potent regulator of miR-29a processing and its inactivation directly affects miR-29a targets. We provide an extended database of RBPs that interact with pre-miRNAs in extracts of different cell types, highlighting a widespread layer of co- and posttranscriptional regulation of miRNA biogenesis. [Display omitted] •A large-scale biochemical screen identifies a broad layer of RBP-miRNA interactions•Loop and stem regions of miRNA precursors can specifically be recognized by RBPs•Depletion of identified RBPs can positively or negatively affect miRNA levels•RBPs can indirectly modulate mRNA expression by regulating mature miRNA levels RNA-binding proteins (RBPs) can bind miRNA precursors and regulate their expression. Treiber et al. have identified protein interactors of more than 70 miRNA precursors in a large number of human cell lines. Depletion of distinct RBPs changes mature miRNA levels and thus indirectly modulates miRNA target mRNA expression levels.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1097-2765eISSN: 1097-4164DOI: 10.1016/j.molcel.2017.03.014Titel-ID: cdi_proquest_miscellaneous_1891146118
- Format
- –
- Schlagworte
- A549 Cells, Binding Sites, CRISPR-Cas Systems, Databases, Genetic, DEAD-box RNA Helicases - metabolism, Gene Expression Regulation, Genomics - methods, HEK293 Cells, HeLa Cells, Hep G2 Cells, High-Throughput Nucleotide Sequencing, Humans, Jurkat Cells, LIN28, MCF-7 Cells, microRNA-guided gene silencing, MicroRNAs - biosynthesis, MicroRNAs - chemistry, MicroRNAs - genetics, Nucleic Acid Conformation, Protein Binding, Proteomics - methods, regulation of microRNA biogenesis, Ribonuclease III - metabolism, RNA binding proteins, RNA Interference, RNA Precursors - biosynthesis, RNA Precursors - chemistry, RNA Precursors - genetics, RNA processing, RNA Processing, Post-Transcriptional, RNA pull-down, RNA, Messenger - biosynthesis, RNA, Messenger - genetics, RNA-Binding Proteins - genetics, RNA-Binding Proteins - metabolism, Sequence Analysis, RNA, siRNA pool, Structure-Activity Relationship, Transcription, Genetic, Transfection, TRIM71, Tripartite Motif Proteins - genetics, Tripartite Motif Proteins - metabolism, Ubiquitin-Protein Ligases - genetics, Ubiquitin-Protein Ligases - metabolism, ZC3H10, ZC3H7