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Accessibility and evolutionary conservation mark bacterial small-rna target-binding regions.

ABSTRACT: Bacterial small noncoding RNAs have attracted much interest in recent years as posttranscriptional regulators of genes involved in diverse pathways. Small RNAs (sRNAs) are 50 to 400 nucleotides long and exert their regulatory function by directly base pairing with mRNA targets to alter their stability and/or affect their translation. This base pairing is achieved through a region of about 10 to 25 nucleotides, which may be located at various positions along different sRNAs. By compiling a data set of experimentally determined target-binding regions of sRNAs and systematically analyzing their properties, we reveal that they are both more evolutionarily conserved and more accessible than random regions. We demonstrate the use of these properties for computational identification of sRNA target-binding regions with high specificity and sensitivity. Our results show that these predicted regions are likely to base pair with known targets of an sRNA, suggesting that pointing out these regions in a specific sRNA can help in searching for its targets.

SUBMITTER: Peer A

PROVIDER: S-EPMC3067639 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Accessibility and evolutionary conservation mark bacterial small-rna target-binding regions.

Peer Asaf A Margalit Hanah H

Journal of bacteriology 20110128 7

Bacterial small noncoding RNAs have attracted much interest in recent years as posttranscriptional regulators of genes involved in diverse pathways. Small RNAs (sRNAs) are 50 to 400 nucleotides long and exert their regulatory function by directly base pairing with mRNA targets to alter their stability and/or affect their translation. This base pairing is achieved through a region of about 10 to 25 nucleotides, which may be located at various positions along different sRNAs. By compiling a data s ...[more]

PMID: 21278294

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Project description:Reprogramming of a gene's expression pattern by acquisition and loss of sequences recognized by specific regulatory RNA binding proteins may be a major mechanism in the evolution of biological regulatory programs. We identified that RNA targets of Puf3 orthologs have been conserved over 100-500 million years of evolution in five eukaryotic lineages. Focusing on Puf proteins and their targets across 80 fungi, we constructed a parsimonious model for their evolutionary history. This model entails extensive and coordinated changes in the Puf targets as well as changes in the number of Puf genes and alterations of RNA binding specificity including that: 1) Binding of Puf3 to more than 200 RNAs whose protein products are predominantly involved in the production and organization of mitochondrial complexes predates the origin of budding yeasts and filamentous fungi and was maintained for 500 million years, throughout the evolution of budding yeast. 2) In filamentous fungi, remarkably, more than 150 of the ancestral Puf3 targets were gained by Puf4, with one lineage maintaining both Puf3 and Puf4 as regulators and a sister lineage losing Puf3 as a regulator of these RNAs. The decrease in gene expression of these mRNAs upon deletion of Puf4 in filamentous fungi (N. crassa) in contrast to the increase upon Puf3 deletion in budding yeast (S. cerevisiae) suggests that the output of the RNA regulatory network is different with Puf4 in filamentous fungi than with Puf3 in budding yeast. 3) The coregulated Puf4 target set in filamentous fungi expanded to include mitochondrial genes involved in the tricarboxylic acid (TCA) cycle and other nuclear-encoded RNAs with mitochondrial function not bound by Puf3 in budding yeast, observations that provide additional evidence for substantial rewiring of post-transcriptional regulation. 4) Puf3 also expanded and diversified its targets in filamentous fungi, gaining interactions with the mRNAs encoding the mitochondrial electron transport chain (ETC) complex I as well as hundreds of other mRNAs with nonmitochondrial functions. The many concerted and conserved changes in the RNA targets of Puf proteins strongly support an extensive role of RNA binding proteins in coordinating gene expression, as originally proposed by Keene. Rewiring of Puf-coordinated mRNA targets and transcriptional control of the same genes occurred at different points in evolution, suggesting that there have been distinct adaptations via RNA binding proteins and transcription factors. The changes in Puf targets and in the Puf proteins indicate an integral involvement of RNA binding proteins and their RNA targets in the adaptation, reprogramming, and function of gene expression.

Project description:BACKGROUND: Molecular recognition features (MoRFs) are short binding regions located in longer intrinsically disordered protein regions. Although these short regions lack a stable structure in the natural state, they readily undergo disorder-to-order transitions upon binding to their partner molecules. MoRFs play critical roles in the molecular interaction network of a cell, and are associated with many human genetic diseases. Therefore, identification of MoRFs is an important step in understanding functional aspects of these proteins and in finding applications in drug design. RESULTS: Here, we propose a novel method for identifying MoRFs, named as MFSPSSMpred (Masked, Filtered and Smoothed Position-Specific Scoring Matrix-based Predictor). Firstly, a masking method is used to calculate the average local conservation scores of residues within a masking-window length in the position-specific scoring matrix (PSSM). Then, the scores below the average are filtered out. Finally, a smoothing method is used to incorporate the features of flanking regions for each residue to prepare the feature sets for prediction. Our method employs no predicted results from other classifiers as input, i.e., all features used in this method are extracted from the PSSM of sequence only. Experimental results show that, comparing with other methods tested on the same datasets, our method achieves the best performance: achieving 0.004~0.079 higher AUC than other methods when tested on TEST419, and achieving 0.045~0.212 higher AUC than other methods when tested on TEST2012. In addition, when tested on an independent membrane proteins-related dataset, MFSPSSMpred significantly outperformed the existing predictor MoRFpred. CONCLUSIONS: This study suggests that: 1) amino acid composition and physicochemical properties in the flanking regions of MoRFs are very different from those in the general non-MoRF regions; 2) MoRFs contain both highly conserved residues and highly variable residues and, on the whole, are highly locally conserved; and 3) combining contextual information with local conservation information of residues facilitates the prediction of MoRFs.

Dataset Information

Accessibility and evolutionary conservation mark bacterial small-rna target-binding regions.

Publications

Accessibility and evolutionary conservation mark bacterial small-rna target-binding regions.

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