A Compendium of RNA-Binding Proteins that Regulate MicroRNA Biogenesis

作者：Treiber Thomas; Treiber Nora; Plessmann Uwe; Harlander Simone; Daiss Julia Lisa; Eichner Norbert; Lehmann Gerhard; Schall Kevin; Urlaub Henning; Meister Gunter^*

来源：Molecular Cell, 2017, 66(2): 270-+.

DOI：10.1016/j.molcel.2017.03.014

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.

• 出版日期2017-4-20