scholarly journals Faculty Opinions recommendation of RNA-binding proteins distinguish between similar sequence motifs to promote targeted deadenylation by Ccr4-Not.

2019 ◽  
Author(s):  
Traci Hall
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Sequence Motifs ◽  
Similar Sequence

scholarly journals RNA-binding proteins distinguish between similar sequence motifs to promote targeted deadenylation by Ccr4-Not

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Michael W Webster ◽  
James AW Stowell ◽  
Lori A Passmore
Keyword(s):  
Mrna Stability ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Low Complexity ◽  
Dissociation Rate ◽  
Sequence Motifs ◽  
Similar Sequence ◽  
Mrna Targets

The Ccr4-Not complex removes mRNA poly(A) tails to regulate eukaryotic mRNA stability and translation. RNA-binding proteins contribute to specificity by interacting with both Ccr4-Not and target mRNAs, but this is not fully understood. Here, we reconstitute accelerated and selective deadenylation of RNAs containing AU-rich elements (AREs) and Pumilio-response elements (PREs). We find that the fission yeast homologues of Tristetraprolin/TTP and Pumilio/Puf (Zfs1 and Puf3) interact with Ccr4-Not via multiple regions within low-complexity sequences, suggestive of a multipartite interface that extends beyond previously defined interactions. Using a two-color assay to simultaneously monitor poly(A) tail removal from different RNAs, we demonstrate that Puf3 can distinguish between RNAs of very similar sequence. Analysis of binding kinetics reveals that this is primarily due to differences in dissociation rate constants. Consequently, motif quality is a major determinant of mRNA stability for Puf3 targets in vivo and can be used for the prediction of mRNA targets.

scholarly journals A unique ribonucleoprotein complex assembles preferentially on ecdysone-responsive sites in Drosophila melanogaster.

1993 ◽  
Vol 13 (9) ◽  
pp. 5323-5330 ◽  
Author(s):  
S A Amero ◽  
M J Matunis ◽  
E L Matunis ◽  
J W Hockensmith ◽  
G Raychaudhuri ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Polytene Chromosomes ◽  
Cell Extract ◽  
Sequence Motifs ◽  
Drosophila Cell ◽  
Rnase Digestion

The protein on ecdysone puffs (PEP) is associated preferentially with active ecdysone-inducible puffs on Drosophila polytene chromosomes and contains sequence motifs characteristic of transcription factors and RNA-binding proteins (S. A. Amero, S. C. R. Elgin, and A. L. Beyer, Genes Dev. 5:188-200, 1991). PEP is associated with RNA in vivo, as demonstrated here by the sensitivity of PEP-specific chromosomal immunostaining in situ to RNase digestion and by the immunopurification of PEP in Drosophila cell extract with heterogeneous nuclear ribonucleoprotein (hnRNP) complexes. As revealed by sequential immunostaining, PEP is found on a subset of chromosomal sites bound by the HRB (heterogeneous nuclear RNA-binding) proteins, which are basic Drosophila hnRNPs. These observations lead us to suggest that a unique, PEP-containing hnRNP complex assembles preferentially on the transcripts of ecdysone-regulated genes in Drosophila melanogaster presumably to expedite the transcription and/or processing of these transcripts.

scholarly journals Inferring Sequence-Structure Preferences of RNA-Binding Proteins with Convolutional Residual Networks

2018 ◽  
Author(s):  
Peter K. Koo ◽  
Praveen Anand ◽  
Steffan B. Paul ◽  
Sean R. Eddy
Keyword(s):  
Rna Structure ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Sequence Data ◽  
Synthetic Data ◽  
Sequence Motifs ◽  
Negative Effects ◽  
Interpretable Model ◽  
Saliency Analysis

AbstractTo infer the sequence and RNA structure specificities of RNA-binding proteins (RBPs) from experiments that enrich for bound sequences, we introduce a convolutional residual network which we call ResidualBind. ResidualBind significantly outperforms previous methods on experimental data from many RBP families. We interrogate ResidualBind to identify what features it has learned from high-affinity sequences with saliency analysis along with 1st-order and 2nd-orderin silicomutagenesis. We show that in addition to sequence motifs, ResidualBind learns a model that includes the number of motifs, their spacing, and both positive and negative effects of RNA structure context. Strikingly, ResidualBind learns RNA structure context, including detailed base-pairing relationships, directly from sequence data, which we confirm on synthetic data. ResidualBind is a powerful, flexible, and interpretable model that can uncovercis-recognition preferences across a broad spectrum of RBPs.

scholarly journals Identifying the sequence specificities of circRNA-binding proteins based on a capsule network architecture

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhengfeng Wang ◽  
Xiujuan Lei
Keyword(s):  
Binding Sites ◽  
Network Architecture ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rnas ◽  
Sequence Motifs ◽  
Rna Motifs ◽  
Classification Framework ◽  
Bound Sequence

Abstract Background Circular RNAs (circRNAs) are widely expressed in cells and tissues and are involved in biological processes and human diseases. Recent studies have demonstrated that circRNAs can interact with RNA-binding proteins (RBPs), which is considered an important aspect for investigating the function of circRNAs. Results In this study, we design a slight variant of the capsule network, called circRB, to identify the sequence specificities of circRNAs binding to RBPs. In this model, the sequence features of circRNAs are extracted by convolution operations, and then, two dynamic routing algorithms in a capsule network are employed to discriminate between different binding sites by analysing the convolution features of binding sites. The experimental results show that the circRB method outperforms the existing computational methods. Afterwards, the trained models are applied to detect the sequence motifs on the seven circRNA-RBP bound sequence datasets and matched to known human RNA motifs. Some motifs on circular RNAs overlap with those on linear RNAs. Finally, we also predict binding sites on the reported full-length sequences of circRNAs interacting with RBPs, attempting to assist current studies. We hope that our model will contribute to better understanding the mechanisms of the interactions between RBPs and circRNAs. Conclusion In view of the poor studies about the sequence specificities of circRNA-binding proteins, we designed a classification framework called circRB based on the capsule network. The results show that the circRB method is an effective method, and it achieves higher prediction accuracy than other methods.

scholarly journals rec-Y2H matrix screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins

2020 ◽  
Author(s):  
Benjamin Lang ◽  
Jae-Seong Yang ◽  
Mireia Garriga-Canut ◽  
Silvia Speroni ◽  
Maria Gili ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Interaction Networks ◽  
Sequence Motifs ◽  
Protein Protein Interactions ◽  
Binding Interaction ◽  
Transcriptional Gene Regulation

AbstractRNA-binding proteins (RBPs) are crucial factors of post-transcriptional gene regulation and their modes of action are intensely investigated. At the center of attention are RNA motifs that guide where RBPs bind. However, sequence motifs are often poor predictors of RBP-RNA interactions in vivo. It is hence believed that many RBPs recognize RNAs as complexes, to increase specificity and regulatory possibilities. To probe the potential for complex formation among RBPs, we assembled a library of 978 mammalian RBPs and used rec-Y2H screening to detect direct interactions between RBPs, sampling > 600 K interactions. We discovered 1994 new interactions and demonstrate that interacting RBPs bind RNAs adjacently in vivo. We further find that the mRNA binding region and motif preferences of RBPs can deviate, depending on their adjacently binding interaction partners. Finally, we reveal novel RBP interaction networks among major RNA processing steps and show that splicing impairing RBP mutations observed in cancer rewire spliceosomal interaction networks.Graphical abstract

Regulation of ELAV/Hu RNA-binding proteins by phosphorylation

2014 ◽  
Vol 42 (4) ◽  
pp. 1147-1151 ◽  
Author(s):  
Ulrike Bräuer ◽  
Emanuela Zaharieva ◽  
Matthias Soller
Keyword(s):  
Cellular Localization ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Sequence Motifs ◽  
Functional Diversification ◽  
Embryonic Lethal ◽  
Hu Proteins ◽  
Abnormal Visual

ELAV (embryonic lethal/abnormal visual system)/Hu proteins comprise a family of highly related neuronal RBPs (RNA-binding proteins) involved in many aspects of mRNA processing. Although they bind to highly similar short sequence motifs, they have acquired diverse functions suggesting that cellular signalling is important for their functional diversification. Indeed, ELAV/Hu proteins harbour many phosphorylatable amino acids. In the present article, we review our current knowledge about phosphorylation of ELAV/Hu proteins and how phosphorylation affects cellular localization of ELAV/Hu proteins and their binding to RNA.

scholarly journals Principles of mRNA targeting via the Arabidopsis m6A-binding protein ECT2

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Laura Arribas-Hernández ◽  
Sarah Rennie ◽  
Tino Köster ◽  
Carlotta Porcelli ◽  
Martin Lewinski ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Activity ◽  
Sequence Motifs ◽  
Intrinsically Disordered ◽  
Eukaryotic Gene ◽  
Yth Domain ◽  
Nucleotide Resolution ◽  
Mrna Targeting

Specific recognition of N6-methyladenosine (m6A) in mRNA by RNA-binding proteins containing a YT521-B homology (YTH) domain is important in eukaryotic gene regulation. The Arabidopsis YTH-domain protein ECT2 is thought to bind to mRNA at URU(m6A)Y sites, yet RR(m6A)CH is the canonical m6A consensus site in all eukaryotes and ECT2 functions require m6A binding activity. Here, we apply iCLIP (individual-nucleotide resolution cross-linking and immunoprecipitation) and HyperTRIBE (targets of RNA-binding proteins identified by editing) to define high-quality target sets of ECT2, and analyze the patterns of enriched sequence motifs around ECT2 crosslink sites. Our analyses show that ECT2 does in fact bind to RR(m6A)CH. Pyrimidine-rich motifs are enriched around, but not at m6A-sites, reflecting a preference for N6-adenosine methylation of RRACH/GGAU islands in pyrimidine-rich regions. Such motifs, particularly oligo-U and UNUNU upstream of m6A sites, are also implicated in ECT2 binding via its intrinsically disordered region (IDR). Finally, URUAY-type motifs are enriched at ECT2 crosslink sites, but their distinct properties suggest function as sites of competition between binding of ECT2 and as yet unidentified RNA-binding proteins. Our study provides coherence between genetic and molecular studies of m6A-YTH function in plants, and reveals new insight into the mode of RNA recognition by YTH-domain-containing proteins.

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