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Structural basis for terminal loop recognition and processing of pri-miRNA-18a by hnRNP A1

Authors :
Michael Sattler
Max Muehlbauer
Alexander Jussupow
Noemi Fernandez
Javier F. Cáceres
Hamed Kooshapur
André Dallmann
Bernd Simon
Nila Roy Choudhury
Frank Gabel
Gracjan Michlewski
Carlo Camilloni
Publication Year :
2017
Publisher :
Cold Spring Harbor Laboratory, 2017.

Abstract

Post-transcriptional mechanisms play a predominant role in the control of microRNA (miRNA) production. Recognition of the terminal loop of precursor miRNAs by RNA-binding proteins (RBPs) influences their processing; however, the mechanistic and structural basis for how levels of individual or subsets of miRNAs are regulated is mostly unexplored. We previously described a role for hnRNP A1, an RBP implicated in many aspects of RNA processing, as an auxiliary factor that promotes the Microprocessor-mediated processing of pri-mir-18a. Here, we reveal the mechanistic basis for this stimulatory role of hnRNP A1 by combining integrative structural biology with biochemical and functional assays. We demonstrate that hnRNP A1 forms a 1:1 complex with pri-mir-18a that involves binding of both RNA recognition motifs (RRMs) to cognate RNA sequence motifs in the conserved terminal loop of pri-mir-18a. Terminal loop binding induces an allosteric destabilization of base-pairing in the pri-mir-18a stem that promotes its down-stream processing. Our results highlight terminal loop RNA recognition by RNA-binding proteins as a general principle of miRNA biogenesis and regulation.

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....fa843614ddfcd81ba8a9ad012d3152a2
Full Text :
https://doi.org/10.1101/178855