A Distinct, Sequence-Induced Conformation Is Required for Recognition of the Constitutive Decay Element RNA by Roquin

Luca Codutti; Kathrin Leppek; Jan Zálešák; Volker Windeisen; Pawel Masiewicz; Georg Stoecklin; Teresa Carlomagno

doi:10.1016/j.str.2015.06.001

A Distinct, Sequence-Induced Conformation Is Required for Recognition of the Constitutive Decay Element RNA by Roquin

Luca Codutti, Kathrin Leppek, Jan Zálešák, Volker Windeisen, Pawel Masiewicz, Georg Stoecklin, Teresa Carlomagno

Biosciences

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

Abstract

The constitutive decay element (CDE) of tumor necrosis factor α (TNF-α) mRNA (Tnf) represents the prototype of a class of RNA motifs that mediate rapid degradation of mRNAs encoding regulators of the immune response and development. CDE-type RNAs are hairpin structures featuring a tri-nucleotide loop. The protein Roquin recognizes CDE-type stem loops and recruits the Ccr4-Caf1-Not deadenylase complex to the mRNA, thereby inducing its decay. Stem recognition does not involve nucleotide bases; however, there is a strong stem sequence requirement for functional CDEs. Here, we present the solution structures of the natural Tnf CDE and of a CDE mutant with impaired Roquin binding. We find that the two CDEs adopt unique and distinct structures in both the loop and the stem, which explains the ability of Roquin to recognize stem loops in a sequence-specific manner. Our findings result in a relaxed consensus motif for prediction of new CDE stem loops.

Original language	English
Pages (from-to)	1437-1447
Number of pages	11
Journal	Structure
Volume	23
Issue number	8
DOIs	https://doi.org/10.1016/j.str.2015.06.001
Publication status	Published - 4 Aug 2015

Bibliographical note

Keywords

Animals
Base Pairing
Base Sequence
Binding Sites
Cloning, Molecular
Crystallography, X-Ray
Escherichia coli/genetics
Gene Expression
HEK293 Cells
Humans
Mice
Models, Molecular
Molecular Sequence Data
NIH 3T3 Cells
Nucleic Acid Conformation
Protein Binding
Protein Interaction Domains and Motifs
Protein Structure, Secondary
RNA Stability
RNA, Messenger/chemistry
RNA-Binding Proteins/chemistry
Recombinant Proteins/chemistry
Ubiquitin-Protein Ligases/chemistry

Access to Document

10.1016/j.str.2015.06.001

Cite this

@article{af88610df6894f3fa626da746476e689,

title = "A Distinct, Sequence-Induced Conformation Is Required for Recognition of the Constitutive Decay Element RNA by Roquin",

abstract = "The constitutive decay element (CDE) of tumor necrosis factor α (TNF-α) mRNA (Tnf) represents the prototype of a class of RNA motifs that mediate rapid degradation of mRNAs encoding regulators of the immune response and development. CDE-type RNAs are hairpin structures featuring a tri-nucleotide loop. The protein Roquin recognizes CDE-type stem loops and recruits the Ccr4-Caf1-Not deadenylase complex to the mRNA, thereby inducing its decay. Stem recognition does not involve nucleotide bases; however, there is a strong stem sequence requirement for functional CDEs. Here, we present the solution structures of the natural Tnf CDE and of a CDE mutant with impaired Roquin binding. We find that the two CDEs adopt unique and distinct structures in both the loop and the stem, which explains the ability of Roquin to recognize stem loops in a sequence-specific manner. Our findings result in a relaxed consensus motif for prediction of new CDE stem loops.",

keywords = "Animals, Base Pairing, Base Sequence, Binding Sites, Cloning, Molecular, Crystallography, X-Ray, Escherichia coli/genetics, Gene Expression, HEK293 Cells, Humans, Mice, Models, Molecular, Molecular Sequence Data, NIH 3T3 Cells, Nucleic Acid Conformation, Protein Binding, Protein Interaction Domains and Motifs, Protein Structure, Secondary, RNA Stability, RNA, Messenger/chemistry, RNA-Binding Proteins/chemistry, Recombinant Proteins/chemistry, Ubiquitin-Protein Ligases/chemistry",

author = "Luca Codutti and Kathrin Leppek and Jan Z{\'a}le{\v s}{\'a}k and Volker Windeisen and Pawel Masiewicz and Georg Stoecklin and Teresa Carlomagno",

year = "2015",

month = aug,

day = "4",

doi = "10.1016/j.str.2015.06.001",

language = "English",

volume = "23",

pages = "1437--1447",

journal = "Structure",

issn = "0969-2126",

publisher = "Elsevier",

number = "8",

}

TY - JOUR

T1 - A Distinct, Sequence-Induced Conformation Is Required for Recognition of the Constitutive Decay Element RNA by Roquin

AU - Codutti, Luca

AU - Leppek, Kathrin

AU - Zálešák, Jan

AU - Windeisen, Volker

AU - Masiewicz, Pawel

AU - Stoecklin, Georg

AU - Carlomagno, Teresa

PY - 2015/8/4

Y1 - 2015/8/4

N2 - The constitutive decay element (CDE) of tumor necrosis factor α (TNF-α) mRNA (Tnf) represents the prototype of a class of RNA motifs that mediate rapid degradation of mRNAs encoding regulators of the immune response and development. CDE-type RNAs are hairpin structures featuring a tri-nucleotide loop. The protein Roquin recognizes CDE-type stem loops and recruits the Ccr4-Caf1-Not deadenylase complex to the mRNA, thereby inducing its decay. Stem recognition does not involve nucleotide bases; however, there is a strong stem sequence requirement for functional CDEs. Here, we present the solution structures of the natural Tnf CDE and of a CDE mutant with impaired Roquin binding. We find that the two CDEs adopt unique and distinct structures in both the loop and the stem, which explains the ability of Roquin to recognize stem loops in a sequence-specific manner. Our findings result in a relaxed consensus motif for prediction of new CDE stem loops.

AB - The constitutive decay element (CDE) of tumor necrosis factor α (TNF-α) mRNA (Tnf) represents the prototype of a class of RNA motifs that mediate rapid degradation of mRNAs encoding regulators of the immune response and development. CDE-type RNAs are hairpin structures featuring a tri-nucleotide loop. The protein Roquin recognizes CDE-type stem loops and recruits the Ccr4-Caf1-Not deadenylase complex to the mRNA, thereby inducing its decay. Stem recognition does not involve nucleotide bases; however, there is a strong stem sequence requirement for functional CDEs. Here, we present the solution structures of the natural Tnf CDE and of a CDE mutant with impaired Roquin binding. We find that the two CDEs adopt unique and distinct structures in both the loop and the stem, which explains the ability of Roquin to recognize stem loops in a sequence-specific manner. Our findings result in a relaxed consensus motif for prediction of new CDE stem loops.

KW - Animals

KW - Base Pairing

KW - Base Sequence

KW - Binding Sites

KW - Cloning, Molecular

KW - Crystallography, X-Ray

KW - Escherichia coli/genetics

KW - Gene Expression

KW - HEK293 Cells

KW - Humans

KW - Mice

KW - Models, Molecular

KW - Molecular Sequence Data

KW - NIH 3T3 Cells

KW - Nucleic Acid Conformation

KW - Protein Binding

KW - Protein Interaction Domains and Motifs

KW - Protein Structure, Secondary

KW - RNA Stability

KW - RNA, Messenger/chemistry

KW - RNA-Binding Proteins/chemistry

KW - Recombinant Proteins/chemistry

KW - Ubiquitin-Protein Ligases/chemistry

U2 - 10.1016/j.str.2015.06.001

DO - 10.1016/j.str.2015.06.001

M3 - Article

C2 - 26165594

SN - 0969-2126

VL - 23

SP - 1437

EP - 1447

JO - Structure

JF - Structure

IS - 8

ER -

A Distinct, Sequence-Induced Conformation Is Required for Recognition of the Constitutive Decay Element RNA by Roquin

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this