TY  - JOUR
AU  - Codutti, Luca
AU  - Leppek, Kathrin
AU  - Zálešák, Jan
AU  - Windeisen, Volker
AU  - Masiewicz, Pawel
AU  - Stoecklin, Georg
AU  - Carlomagno, Teresa
TI  - A Distinct, Sequence-Induced Conformation Is Required for Recognition of the Constitutive Decay Element RNA by Roquin.
JO  - Structure
VL  - 23
IS  - 8
SN  - 0969-2126
CY  - London [u.a.]
PB  - Elsevier Science
M1  - DKFZ-2017-02389
SP  - 1437 - 1447
PY  - 2015
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  - RC3H1 protein, human (NLM Chemicals)
KW  - RNA, Messenger (NLM Chemicals)
KW  - RNA-Binding Proteins (NLM Chemicals)
KW  - Recombinant Proteins (NLM Chemicals)
KW  - Ubiquitin-Protein Ligases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26165594
DO  - DOI:10.1016/j.str.2015.06.001
UR  - https://inrepo02.dkfz.de/record/126274
ER  -