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Diverse RNA-binding proteins interact with functionally related sets of RNAs, suggesting an extensive regulatory system.

Hogan DJ, Riordan DP, Gerber AP, Herschlag D, Brown PO - PLoS Biol. (2008)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.

ABSTRACT
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.

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Related in: MedlinePlus

RNA-Binding Proteins Bind mRNAs Encoding Functionally and Cytotopically Related Proteins(A) Enrichment of “cellular component” GO terms (rows) in target sets (1% FDR) of RBPs (columns). The significance of enrichment of the GO term is represented as a heat map (scale is to the left of the figure) in which the color intensity corresponds to the negative log10p-value, calculated using the hypergeometric density distribution function and corrected for multiple hypothesis testing using the Bonferroni method. Only a subset of significantly enriched GO terms are shown. RBPs whose targets are significantly enriched (p ≤ 0.01) for at least one “cellular component” or “biological process” GO term are shown.(B) Same as in (A), except for “biological process” GO terms.
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pbio-0060255-g002: RNA-Binding Proteins Bind mRNAs Encoding Functionally and Cytotopically Related Proteins(A) Enrichment of “cellular component” GO terms (rows) in target sets (1% FDR) of RBPs (columns). The significance of enrichment of the GO term is represented as a heat map (scale is to the left of the figure) in which the color intensity corresponds to the negative log10p-value, calculated using the hypergeometric density distribution function and corrected for multiple hypothesis testing using the Bonferroni method. Only a subset of significantly enriched GO terms are shown. RBPs whose targets are significantly enriched (p ≤ 0.01) for at least one “cellular component” or “biological process” GO term are shown.(B) Same as in (A), except for “biological process” GO terms.

Mentions: Regulatory proteins, including both transcription factors and RBPs, typically regulate sets of targets that share identifiable functional relationships (e.g., [26–29,32,35,52–60]). As a first step toward identifying relationships among RNAs bound by specific RBPs, we searched for gene ontology (GO) terms [61] that were significantly enriched among the targets of each RBP. Twenty-five of the RBPs in this survey were consistently associated with at least ten mRNAs; 13 of these sets of RNA targets specific to an RBP were significantly enriched for at least one “cellular component” GO term (Figure 2A and Table S3), representing a shared subcellular localization or in some instances a protein complex, and 13 of these RBP-specific target sets were significantly enriched for at least one “biological process” GO term (Figure 2B and Table S3).


Diverse RNA-binding proteins interact with functionally related sets of RNAs, suggesting an extensive regulatory system.

Hogan DJ, Riordan DP, Gerber AP, Herschlag D, Brown PO - PLoS Biol. (2008)

RNA-Binding Proteins Bind mRNAs Encoding Functionally and Cytotopically Related Proteins(A) Enrichment of “cellular component” GO terms (rows) in target sets (1% FDR) of RBPs (columns). The significance of enrichment of the GO term is represented as a heat map (scale is to the left of the figure) in which the color intensity corresponds to the negative log10p-value, calculated using the hypergeometric density distribution function and corrected for multiple hypothesis testing using the Bonferroni method. Only a subset of significantly enriched GO terms are shown. RBPs whose targets are significantly enriched (p ≤ 0.01) for at least one “cellular component” or “biological process” GO term are shown.(B) Same as in (A), except for “biological process” GO terms.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2573929&req=5

pbio-0060255-g002: RNA-Binding Proteins Bind mRNAs Encoding Functionally and Cytotopically Related Proteins(A) Enrichment of “cellular component” GO terms (rows) in target sets (1% FDR) of RBPs (columns). The significance of enrichment of the GO term is represented as a heat map (scale is to the left of the figure) in which the color intensity corresponds to the negative log10p-value, calculated using the hypergeometric density distribution function and corrected for multiple hypothesis testing using the Bonferroni method. Only a subset of significantly enriched GO terms are shown. RBPs whose targets are significantly enriched (p ≤ 0.01) for at least one “cellular component” or “biological process” GO term are shown.(B) Same as in (A), except for “biological process” GO terms.
Mentions: Regulatory proteins, including both transcription factors and RBPs, typically regulate sets of targets that share identifiable functional relationships (e.g., [26–29,32,35,52–60]). As a first step toward identifying relationships among RNAs bound by specific RBPs, we searched for gene ontology (GO) terms [61] that were significantly enriched among the targets of each RBP. Twenty-five of the RBPs in this survey were consistently associated with at least ten mRNAs; 13 of these sets of RNA targets specific to an RBP were significantly enriched for at least one “cellular component” GO term (Figure 2A and Table S3), representing a shared subcellular localization or in some instances a protein complex, and 13 of these RBP-specific target sets were significantly enriched for at least one “biological process” GO term (Figure 2B and Table S3).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus