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

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Original languageEnglish
JournalNature Communications
Early online date26 Jun 2018
DOIs
Publication statusE-pub ahead of print - 26 Jun 2018

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 basis for how levels of individual
or subsets of miRNAs are regulated is mostly unexplored. We previously showed that hnRNP
A1, an RBP implicated in many aspects of RNA processing, acts as an auxiliary factor that
promotes the Microprocessor-mediated processing of pri-mir-18a. Here, by using an
integrative structural biology approach, we show that hnRNP A1 forms a 1:1 complex with primir-
18a where both RNA recognition motifs (RRMs) bind to cognate RNA sequence motifs in
the 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 RBPs as a potential general principle of miRNA
biogenesis and regulation.

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