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PDBsum entry 6dcl
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RNA binding protein/RNA
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PDB id
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6dcl
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References listed in PDB file
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Key reference
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Title
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Structural basis for terminal loop recognition and stimulation of pri-Mirna-18a processing by hnrnp a1.
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Authors
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H.Kooshapur,
N.R.Choudhury,
B.Simon,
M.Mühlbauer,
A.Jussupow,
N.Fernandez,
A.N.Jones,
A.Dallmann,
F.Gabel,
C.Camilloni,
G.Michlewski,
J.F.Caceres,
M.Sattler.
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Ref.
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Nat Commun, 2018,
9,
2479.
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PubMed id
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Abstract
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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 pri-mir-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 downstream processing. Our results highlight terminal
loop RNA recognition by RBPs as a potential general principle of miRNA
biogenesis and regulation.
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