6SJD

ZC3H12B-ribonuclease domain bound to RNA

Summary for 6SJD

• Entry DOI: 10.2210/pdb6sjd/pdb
• Descriptor: Probable ribonuclease ZC3H12B, RNA (5'-R(*UP*GP*CP*GP*AP*CP*AP*GP*UP*CP*GP*GP*UP*AP*GP*CP*A)-3'), MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: pin rnase domain, splice donor sequence rna, degradation of cytoplasmic viral and/or unspliced transcripts, rna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 48559.30

Authors

Morgunova, E.,Bourenkov, G.,Taipale, J. (deposition date: 2019-08-13, release date: 2020-07-22, Last modification date: 2024-01-24)

Primary citation

Jolma, A.,Zhang, J.,Mondragon, E.,Morgunova, E.,Kivioja, T.,Laverty, K.U.,Yin, Y.,Zhu, F.,Bourenkov, G.,Morris, Q.,Hughes, T.R.,Maher 3rd, L.J.,Taipale, J.
Binding specificities of human RNA-binding proteins toward structured and linear RNA sequences.
Genome Res., 30:962-973, 2020

PubMed Abstract: RNA-binding proteins (RBPs) regulate RNA metabolism at multiple levels by affecting splicing of nascent transcripts, RNA folding, base modification, transport, localization, translation, and stability. Despite their central role in RNA function, the RNA-binding specificities of most RBPs remain unknown or incompletely defined. To address this, we have assembled a genome-scale collection of RBPs and their RNA-binding domains (RBDs) and assessed their specificities using high-throughput RNA-SELEX (HTR-SELEX). Approximately 70% of RBPs for which we obtained a motif bound to short linear sequences, whereas ∼30% preferred structured motifs folding into stem-loops. We also found that many RBPs can bind to multiple distinctly different motifs. Analysis of the matches of the motifs in human genomic sequences suggested novel roles for many RBPs. We found that three cytoplasmic proteins-ZC3H12A, ZC3H12B, and ZC3H12C-bound to motifs resembling the splice donor sequence, suggesting that these proteins are involved in degradation of cytoplasmic viral and/or unspliced transcripts. Structural analysis revealed that the RNA motif was not bound by the conventional C3H1 RNA-binding domain of ZC3H12B. Instead, the RNA motif was bound by the ZC3H12B's PilT N terminus (PIN) RNase domain, revealing a potential mechanism by which unconventional RBDs containing active sites or molecule-binding pockets could interact with short, structured RNA molecules. Our collection containing 145 high-resolution binding specificity models for 86 RBPs is the largest systematic resource for the analysis of human RBPs and will greatly facilitate future analysis of the various biological roles of this important class of proteins.

PubMed: 32703884
DOI: 10.1101/gr.258848.119

Experimental method

X-RAY DIFFRACTION (3.29 Å)