RNA–protein interactions in human health and disease

Khalil, Ahmad M.; Rinn, John L.

doi:10.1016/j.semcdb.2011.02.016

Cited by 129 publications

(108 citation statements)

References 76 publications

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“…In fact, we found that the 10% most highly structured transcripts were found at significantly lower levels on average compared with the least folded Arabidopsis mRNAs (see Supplemental Figure 3A online). This was somewhat surprising because RNA binding proteins tend to bind highly structured regions of mRNAs and often have a stabilizing effect on bound transcripts (Keene, 2001;Glisovic et al, 2008;Khalil and Rinn, 2011;Konig et al, 2012). However, our data suggest that highly structured transcripts are often tightly regulated, pathogen-responsive genes in Arabidopsis ( Figure 1C).…”

Section: Gene Expression Regulation By Rna Secondary Structure In Aramentioning

confidence: 99%

“…In fact, it is known that rRNAs must form intricate secondary structures to enable proper formation of functional ribosomes (Trappl and Polacek, 2011). More recently, it has been shown that the structure of long noncoding RNAs is most likely necessary for their function in gene expression regulation (Khalil and Rinn, 2011;Ulitsky et al, 2011;Wan et al, 2011). Thus, the secondary structure of RNAs is required for the functionality of these molecules.…”

Section: Introductionmentioning

confidence: 99%

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Regulatory Impact of RNA Secondary Structure across the Arabidopsis Transcriptome

et al. 2012

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The secondary structure of an RNA molecule plays an integral role in its maturation, regulation, and function. However, the global influence of this feature on plant gene expression is still largely unclear. Here, we use a high-throughput, sequencingbased, structure-mapping approach in conjunction with transcriptome-wide sequencing of rRNA-depleted (RNA sequencing), small RNA, and ribosome-bound RNA populations to investigate the impact of RNA secondary structure on gene expression regulation in Arabidopsis thaliana. From this analysis, we find that highly unpaired and paired RNAs are strongly correlated with euchromatic and heterochromatic epigenetic histone modifications, respectively, providing evidence that secondary structure is necessary for these RNA-mediated posttranscriptional regulatory pathways. Additionally, we uncover key structural patterns across protein-coding transcripts that indicate RNA folding demarcates regions of protein translation and likely affects microRNA-mediated regulation of mRNAs in this model plant. We further reveal that RNA folding is significantly anticorrelated with overall transcript abundance, which is often due to the increased propensity of highly structured mRNAs to be degraded and/or processed into small RNAs. Finally, we find that secondary structure affects mRNA translation, suggesting that this feature regulates plant gene expression at multiple levels. These findings provide a global assessment of RNA folding and its significant regulatory effects in a plant transcriptome.

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Section: Gene Expression Regulation By Rna Secondary Structure In Aramentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulatory Impact of RNA Secondary Structure across the Arabidopsis Transcriptome

et al. 2012

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“…RNA-protein interactions (RPIs) also play important roles in human health and diseases [4], as well as in viral replication [5], and pathogen resistance in plants [6]. Even though the human genome contains more than 400 known or predicted RBPs [7,8], the structures of RNA-protein complexes and the roles of RPIs in post-transcriptional regulatory networks [1,9], are much less well characterized than the DNA-protein complexes involved in transcriptional regulation.…”

Section: Introductionmentioning

confidence: 99%

Computational Tools for Investigating RNA-Protein Interaction Partners

Muppirala¹,

Lewis

Dobbs

2013

J Comput Sci Syst Biol

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RNA-protein interactions are important in a wide variety of cellular and developmental processes. Recently, high-throughput experiments have begun to provide valuable information about RNA partners and binding sites for many RNA-binding proteins (RBPs), but these experiments are expensive and time consuming. Thus, computational methods for predicting RNA-Protein interactions (RPIs) can be valuable tools for identifying potential interaction partners of a given protein or RNA, and for identifying likely interfacial residues in RNAprotein complexes. This review focuses on the "partner prediction" problem and summarizes available computational methods, web servers and databases that are devoted to it. New computational tools for addressing the related "interface prediction" problem are also discussed. Together, these computational methods for investigating RNA-protein interactions provide the basis for new strategies for integrating RNAprotein interactions into existing genetic and developmental regulatory networks, an important goal of future research.

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“…The discovery of significant functional roles for long noncoding RNAs (ncRNAs) in human cells with respect to their association with chromatin-modifying complexes (13,15,16) suggested to us that KSHV PAN RNA may function to control gene expression in a targeted but global manner. These previously described ncRNAs play key regulatory roles, such as regulating the activity or localization of proteins and acting as scaffolds to regulate gene expression (11,28).…”

mentioning

confidence: 99%