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Identification of RNA recognition elements in the Saccharomyces cerevisiae transcriptome.

Riordan DP, Herschlag D, Brown PO - Nucleic Acids Res. (2010)

Bottom Line: We computationally analyzed the sequences of Saccharomyces cerevisiae mRNAs bound in vivo by 29 specific RBPs, identifying eight novel candidate motifs and confirming or extending six earlier reported recognition elements.Biochemical selections for RNA sequences selectively recognized by 12 yeast RBPs yielded novel motifs bound by Pin4, Nsr1, Hrb1, Gbp2, Sgn1 and Mrn1, and recovered the known recognition elements for Puf3, She2, Vts1 and Whi3.Most of the RNA elements we uncovered were associated with coherent mRNA expression changes and were significantly conserved in related yeasts, supporting their functional importance and suggesting that the corresponding RNA-protein interactions are evolutionarily conserved.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California, USA. driordan@stanford.edu

ABSTRACT
Post-transcriptional regulation of gene expression, including mRNA localization, translation and decay, is ubiquitous yet still largely unexplored. How is the post-transcriptional regulatory program of each mRNA encoded in its sequence? Hundreds of specific RNA-binding proteins (RBPs) appear to play roles in mediating the post-transcriptional regulatory program, akin to the roles of specific DNA-binding proteins in transcription. As a step toward decoding the regulatory programs encoded in each mRNA, we focused on specific mRNA-protein interactions. We computationally analyzed the sequences of Saccharomyces cerevisiae mRNAs bound in vivo by 29 specific RBPs, identifying eight novel candidate motifs and confirming or extending six earlier reported recognition elements. Biochemical selections for RNA sequences selectively recognized by 12 yeast RBPs yielded novel motifs bound by Pin4, Nsr1, Hrb1, Gbp2, Sgn1 and Mrn1, and recovered the known recognition elements for Puf3, She2, Vts1 and Whi3. Most of the RNA elements we uncovered were associated with coherent mRNA expression changes and were significantly conserved in related yeasts, supporting their functional importance and suggesting that the corresponding RNA-protein interactions are evolutionarily conserved.

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mRNA expression changes associated with RNA motifs. A heatmap illustrates the degree to which the relative expression levels of mRNAs containing each of the identified RNA sequence motifs (rows) changed under each of the environmental stress conditions shown (columns). For each motif and each stress condition we calculated the t-value measuring how much the average expression change of mRNAs with motif sites deviated from its expected value by chance. Relative increases in average mRNA expression levels are colored in red, and relative decreases are colored in green. For exact data values and supporting details see Supplementary Data S5.
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Figure 5: mRNA expression changes associated with RNA motifs. A heatmap illustrates the degree to which the relative expression levels of mRNAs containing each of the identified RNA sequence motifs (rows) changed under each of the environmental stress conditions shown (columns). For each motif and each stress condition we calculated the t-value measuring how much the average expression change of mRNAs with motif sites deviated from its expected value by chance. Relative increases in average mRNA expression levels are colored in red, and relative decreases are colored in green. For exact data values and supporting details see Supplementary Data S5.

Mentions: To investigate the potential roles of the identified RNA motifs in condition-specific regulation of mRNA abundance, we integrated our motif results with a large-scale compendium of stress-induced gene expression programs (33). For each environmental stress condition and each RNA motif, we calculated a t-statistic value (34) as a measure of the direction and significance of coherent changes in expression of the mRNAs that share a putative RBP recognition element (Figure 5). This analysis revealed numerous conditions under which sets of genes defined by a common RNA motif showed coherent stress-induced changes in mRNA abundance [263 motif-condition pairs for which (t-value) > 4, FDR < 10−3].Figure 5.


Identification of RNA recognition elements in the Saccharomyces cerevisiae transcriptome.

Riordan DP, Herschlag D, Brown PO - Nucleic Acids Res. (2010)

mRNA expression changes associated with RNA motifs. A heatmap illustrates the degree to which the relative expression levels of mRNAs containing each of the identified RNA sequence motifs (rows) changed under each of the environmental stress conditions shown (columns). For each motif and each stress condition we calculated the t-value measuring how much the average expression change of mRNAs with motif sites deviated from its expected value by chance. Relative increases in average mRNA expression levels are colored in red, and relative decreases are colored in green. For exact data values and supporting details see Supplementary Data S5.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3045596&req=5

Figure 5: mRNA expression changes associated with RNA motifs. A heatmap illustrates the degree to which the relative expression levels of mRNAs containing each of the identified RNA sequence motifs (rows) changed under each of the environmental stress conditions shown (columns). For each motif and each stress condition we calculated the t-value measuring how much the average expression change of mRNAs with motif sites deviated from its expected value by chance. Relative increases in average mRNA expression levels are colored in red, and relative decreases are colored in green. For exact data values and supporting details see Supplementary Data S5.
Mentions: To investigate the potential roles of the identified RNA motifs in condition-specific regulation of mRNA abundance, we integrated our motif results with a large-scale compendium of stress-induced gene expression programs (33). For each environmental stress condition and each RNA motif, we calculated a t-statistic value (34) as a measure of the direction and significance of coherent changes in expression of the mRNAs that share a putative RBP recognition element (Figure 5). This analysis revealed numerous conditions under which sets of genes defined by a common RNA motif showed coherent stress-induced changes in mRNA abundance [263 motif-condition pairs for which (t-value) > 4, FDR < 10−3].Figure 5.

Bottom Line: We computationally analyzed the sequences of Saccharomyces cerevisiae mRNAs bound in vivo by 29 specific RBPs, identifying eight novel candidate motifs and confirming or extending six earlier reported recognition elements.Biochemical selections for RNA sequences selectively recognized by 12 yeast RBPs yielded novel motifs bound by Pin4, Nsr1, Hrb1, Gbp2, Sgn1 and Mrn1, and recovered the known recognition elements for Puf3, She2, Vts1 and Whi3.Most of the RNA elements we uncovered were associated with coherent mRNA expression changes and were significantly conserved in related yeasts, supporting their functional importance and suggesting that the corresponding RNA-protein interactions are evolutionarily conserved.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California, USA. driordan@stanford.edu

ABSTRACT
Post-transcriptional regulation of gene expression, including mRNA localization, translation and decay, is ubiquitous yet still largely unexplored. How is the post-transcriptional regulatory program of each mRNA encoded in its sequence? Hundreds of specific RNA-binding proteins (RBPs) appear to play roles in mediating the post-transcriptional regulatory program, akin to the roles of specific DNA-binding proteins in transcription. As a step toward decoding the regulatory programs encoded in each mRNA, we focused on specific mRNA-protein interactions. We computationally analyzed the sequences of Saccharomyces cerevisiae mRNAs bound in vivo by 29 specific RBPs, identifying eight novel candidate motifs and confirming or extending six earlier reported recognition elements. Biochemical selections for RNA sequences selectively recognized by 12 yeast RBPs yielded novel motifs bound by Pin4, Nsr1, Hrb1, Gbp2, Sgn1 and Mrn1, and recovered the known recognition elements for Puf3, She2, Vts1 and Whi3. Most of the RNA elements we uncovered were associated with coherent mRNA expression changes and were significantly conserved in related yeasts, supporting their functional importance and suggesting that the corresponding RNA-protein interactions are evolutionarily conserved.

Show MeSH
Related in: MedlinePlus