A Compendium of RNA-Binding Proteins that Regulate MicroRNA Biogenesis

Treiber, Thomas and Treiber, Nora and Plessmann, Uwe and Harlander, Simone and Daiss, Julia-Lisa and Eichner, Norbert and Lehmann, Gerhard and Schall, Kevin and Urlaub, Henning and Meister, Gunter (2017) A Compendium of RNA-Binding Proteins that Regulate MicroRNA Biogenesis. MOLECULAR CELL, 66 (2). 270-+. ISSN 1097-2765, 1097-4164

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: SEQUENCE DETERMINANTS; LIN28-LET-7 PATHWAY; SECONDARY STRUCTURE; GENE-REGULATION; PRE-MICRORNA; HNRNP A1; URIDYLATION; RECOGNITION; DROSOPHILA; TARGET;
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie
Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Dec 2018 13:10
Last Modified: 28 Feb 2019 10:45
URI: https://pred.uni-regensburg.de/id/eprint/1023

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