Prediction of RNA binding proteins comes of age from low resolution to high resolution

Zhao, Huiying; Yang, Yuedong; Zhou, Yaoqi

doi:10.1039/c3mb70167k

Cited by 35 publications

(37 citation statements)

References 71 publications

(129 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many functional riboSNitches in mRNAs are likely to exert their effect by lowering the accessibility to RBPs or regulatory RNAs due to changes in the binding site of a target RNA. Recent in silico analyses of RNA‐binding preferences for a subset of RBPs clearly indicate that structure plays a central role in determining the binding affinity of some RBPs . A majority of RBPs with well‐characterized binding preferences have a high preference for single‐stranded RNA, and are observed to have a significantly lower binding affinity for structured RNA, even if the region contains the sequence motif critical for binding .…”

Section: Rna‐binding Proteins and The Ribosnitchmentioning

confidence: 99%

The potential of the riboSNitch in personalized medicine

et al. 2015

View full text Add to dashboard Cite

RNA conformation plays a significant role in stability, ligand binding, transcription and translation. Single nucleotide variants (SNVs) have the potential to disrupt specific structural elements because RNA folds in a sequence specific manner. A riboSNitch is an element of RNA structure with a specific function that is disrupted by an SNV or SNP (single nucleotide variant or polymorphism; SNVs occur with low frequency in the population, <1%). The riboSNitch is analogous to a riboswitch, where binding of a small molecule rather than mutation alters the structure of the RNA to control gene regulation. RiboSNitches are particularly relevant to interpreting the results of genome-wide association studies (GWAS). Often GWAS identify SNPs associated with a phenotype mapping to non-coding regions of the genome. Since a majority of the human genome is transcribed, significant subsets of GWAS SNPs are putative riboSNitches. The extent to which the transcriptome is tolerant of SNP-induced structure change is still poorly understood. Recent advances in ultra-high throughput structure probing begin to reveal the structural complexities of mutation induced structure change. This review summarizes our current understanding of SNV and SNP-induced structure change in the human transcriptome and discusses the importance of riboSNitch discovery in interpreting GWAS results and massive sequencing projects.

show abstract

Section: Rna‐binding Proteins and The Ribosnitchmentioning

confidence: 99%

The potential of the riboSNitch in personalized medicine

et al. 2015

View full text Add to dashboard Cite

show abstract

“…SPOT-seq 30 , template-based RNA-binding detection, was more accurate than other sequence or structure-based methods tested in 31…”

Section: Rna Bindingmentioning

confidence: 89%

Prediction of Hfq in actinobacteria

Bora

Ward

Kim

2015

Preprint

View full text Add to dashboard Cite

Hfq is the bacterial orthologue of the eukaryotic (L)Sm family of proteins found across all domains of life and potentially an ancient protein, but it has not been found in all phyletic lines. A careful search successfully identified a distant hfq orthologue in the cyanobacteria leaving the actinobacteria as the major phylum with no known hfq orthologue. A search for hfq in actinobacteria, using domain enhanced searching (DELTA-BLAST) with cyanobacterial hfq, identified a conserved actinobacterial specific protein as remotely homologous. Structural homology modelling using profile matching to fold libraries and ab initio 3D structure determination supports this prediction and suggests module shuffling in the evolution of the actinobacterial hfq. Our results provide the basis to explore this prediction, and exploit it, across diverse taxa with potentially important post-transcriptional regulatory effects in virulence, antibiotic production and interactions in human microbiomes. However, the role of hfq in gram positive bacteria has remained elusive and experimental verification will be challenging.

show abstract

“…A viable alternative to support and extend experimental‐ and sequence similarity–based approaches to elucidate putative RBPs is to use computational methods . A recent review summarizes two classes of methods that produce predictions from protein sequences and from protein structures . These methods not only identify RBPs but many of them also predict RNA binding residues and, in the case of the structure‐based methods, atomic level details of these interactions.…”

Section: Introductionmentioning

confidence: 99%

In Silico Prediction and Validation of Novel RNA Binding Proteins and Residues in the Human Proteome

2018

View full text Add to dashboard Cite

Deciphering a complete landscape of protein-RNA interactions in the human proteome remains an elusive challenge. We computationally elucidate RNA binding proteins (RBPs) using an approach that complements previous efforts. We employ two modern complementary sequence-based methods that provide accurate predictions from the structured and the intrinsically disordered sequences, even in the absence of sequence similarity to the known RBPs. We generate and analyze putative RNA binding residues on the whole proteome scale. Using a conservative setting that ensures low, 5% false positive rate, we identify 1511 putative RBPs that include 281 known RBPs and 166 RBPs that were previously predicted. We empirically demonstrate that these overlaps are statistically significant. We also validate the putative RBPs based on two major hallmarks of their RNA binding residues: high levels of evolutionary conservation and enrichment in charged amino acids. Moreover, we show that the novel RBPs are significantly under-annotated functionally which coincides with the fact that they were not yet found to interact with RNAs. We provide two examples of our novel putative RBPs for which there is recent evidence of their interactions with RNAs. The dataset of novel putative RBPs and RNA binding residues for the future hypothesis generation is provided in the Supporting Information.

show abstract

Prediction of RNA binding proteins comes of age from low resolution to high resolution

Cited by 35 publications

References 71 publications

The potential of the riboSNitch in personalized medicine

The potential of the riboSNitch in personalized medicine

Prediction of Hfq in actinobacteria

In Silico Prediction and Validation of Novel RNA Binding Proteins and Residues in the Human Proteome

Contact Info

Product

Resources

About