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

Hamed Kooshapur; Nila Roy Choudhury; Bernd Simon; Max Mühlbauer; Alexander Jussupow; Noemi Fernandez; Alisha N. Jones; Andre Dallmann; Frank Gabel; Carlo Camilloni; Gracjan Michlewski; Javier F. Caceres; Michael Sattler

doi:10.1038/s41467-018-04871-9

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

Hamed Kooshapur, Nila Roy Choudhury, Bernd Simon, Max Mühlbauer, Alexander Jussupow, Noemi Fernandez, Alisha N. Jones, Andre Dallmann, Frank Gabel, Carlo Camilloni, Gracjan Michlewski, Javier F. Caceres, Michael Sattler

Chemistry

Research output: Contribution to journal › Article › peer-review

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 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.

Original language	English (US)
Article number	2479
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04871-9
State	Published - Dec 1 2018

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/s41467-018-04871-9

Cite this

Kooshapur, H., Choudhury, N. R., Simon, B., Mühlbauer, M., Jussupow, A., Fernandez, N., Jones, A. N., Dallmann, A., Gabel, F., Camilloni, C., Michlewski, G., Caceres, J. F., & Sattler, M. (2018). Structural basis for terminal loop recognition and stimulation of pri-miRNA-18a processing by hnRNP A1. Nature communications, 9(1), Article 2479. https://doi.org/10.1038/s41467-018-04871-9

@article{2a5c50a00a3b45aca03f604aaae1dac4,

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

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 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.",

author = "Hamed Kooshapur and Choudhury, {Nila Roy} and Bernd Simon and Max M{\"u}hlbauer and Alexander Jussupow and Noemi Fernandez and Jones, {Alisha N.} and Andre Dallmann and Frank Gabel and Carlo Camilloni and Gracjan Michlewski and Caceres, {Javier F.} and Michael Sattler",

note = "Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-018-04871-9",

language = "English (US)",

volume = "9",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

TY - JOUR

T1 - Structural basis for terminal loop recognition and stimulation of pri-miRNA-18a processing by hnRNP A1

AU - Kooshapur, Hamed

AU - Choudhury, Nila Roy

AU - Simon, Bernd

AU - Mühlbauer, Max

AU - Jussupow, Alexander

AU - Fernandez, Noemi

AU - Jones, Alisha N.

AU - Dallmann, Andre

AU - Gabel, Frank

AU - Camilloni, Carlo

AU - Michlewski, Gracjan

AU - Caceres, Javier F.

AU - Sattler, Michael

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85049253053&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049253053&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-04871-9

DO - 10.1038/s41467-018-04871-9

M3 - Article

C2 - 29946118

AN - SCOPUS:85049253053

SN - 2041-1723

VL - 9

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 2479

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this