Diverse RNA-Binding Proteins Interact with Functionally Related Sets of RNAs, Suggesting an Extensive Regulatory System

By Daniel J. Hogan, Daniel P. Riordan, André P. Gerber, Daniel Herschlag, Patrick O. Brown. PLoS Biology, 2008

631 citations recorded by the source corpus.

RNA-binding proteins (RBPs) have roles in the regulation of many post-transcriptional steps in gene expression, but relatively few RBPs have been systematically studied. We searched for the RNA targets of 40 proteins in the yeast Saccharomyces cerevisiae: a selective sample of the approximately 600 annotated and predicted RBPs, as well as several proteins not annotated as RBPs. At least 33 of these 40 proteins, including three of the four proteins that were not previously known or predicted to be RBPs, were reproducibly associated with specific sets of a few to several hundred RNAs. Remarkably, many of the RBPs we studied bound mRNAs whose protein products share identifiable functional or cytotopic features. We identified specific sequences or predicted structures significantly enriched in target mRNAs of 16 RBPs. These potential RNA-recognition elements were diverse in sequence, structure, and location: some were found predominantly in 3′-untranslated regions, others in 5′-untranslated regions, some in coding sequences, and many in two or more of these features. Although this study only examined a small fraction of the universe of yeast RBPs, 70% of the mRNA transcriptome had significant associations with at least one of these RBPs, and on average, each distinct yeast mRNA interacted with three of the RBPs, suggesting the potential for a rich, multidimensional network of regulation. These results strongly suggest that combinatorial binding of RBPs to specific recognition elements in mRNAs is a pervasive mechanism for multi-dimensional regulation of their post-transcriptional fate.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/92fc6ba0f743eab5b09800d5efb5d0dd29d31205

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Citations in the corpus

Integrative regulatory mapping indicates that the RNA-binding protein HuR (ELAVL1) couples pre-mRNA processing and mRNA stability (2011, methodology): “…the expression of transcripts encoding functionally related proteins through combinatorial and dynamic interactions (Keene and Tenenbaum, 2002; Hogan et al., 2008). olecular Cell 43, 327–339, August 5, 2011 ª2011 Elsevier Inc. 327 The primary deficiency of RIP-chip is the inability to…”
Predicting RNA-Protein Interactions Using Only Sequence Information (2011, methodology): “[10], and 5,166 randomly generated negative examples of mRNA-protein pairs, Pancaldi and Bähler reported an average accuracy of 70% in 2-fold cross-validation tests using an RF classifier based on 500 trees, and 68% using an SVM classifier using an RBF kernel with optimized parameters [36].”
RBPDB: a database of RNA-binding specificities (2010, background): “There is RNA-binding information for proteins in other species, particularly traditional non-metazoan model systems such as yeast (39) and Arabidopsis [e.g. (40)], and also bacteria.”
Revealing protein–lncRNA interaction (2015, background): “several RNAs, and a given RNA often interacts with more than one RBP [32].”
Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila (2015, neutral): “A number of factors have been studied in vivo but largely within small-scale studies (e.g., Hogan et al. 2008; Zhao et al. 2010; Brazao et al. 2012; Chen et al. 2014b; Lu et al. 2014).”
Resolving RNA complexity to decipher regulatory rules governing biological networks (2010, neutral): “melanogaster and iron response pathways in vertebrate cells in the 1990s were followed by more general hypotheses of functionally coherent networks in yeast, tissue culture cells and mouse brain, as recently discusse”