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A compendium of RNA-binding proteins that regulate microRNA biogenesis.

MPG-Autoren
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Plessmann,  U.
Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society;

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Urlaub,  H.
Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society;

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Zitation

Treiber, T., Treiber, N., Plessmann, U., Harlander, S., Daiss, J. L., Eichner, N., et al. (2017). A compendium of RNA-binding proteins that regulate microRNA biogenesis. Molecular Cell, 66(2), 270-284. doi:10.1016/j.molcel.2017.03.014.


Zitierlink: https://hdl.handle.net/11858/00-001M-0000-002D-33CF-F
Zusammenfassung
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 similar to 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.