The RNA Base-Pairing Problem and Base-Pairing Solutions

Lu, Zhipeng; Chang, Howard Y.

doi:10.1101/cshperspect.a034926

Cited by 32 publications

(37 citation statements)

References 87 publications

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“…The application of these methods will be instrumental in the analysis of other RNP complexes. More importantly, the discovery of compact RNP domains set the stage for focused in vitro studies of these domains through purification reconstitution and structure analysis using physical methods 53 . Multiple previous studies have analyzed the XIST RNA, either in part or in its entirety, using various methods 18,19,[54][55][56][57] .…”

Section: Discussionmentioning

confidence: 99%

Structural modularity of the XIST ribonucleoprotein complex

Guo

Wei

et al. 2020

Nat Commun

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Long noncoding RNAs are thought to regulate gene expression by organizing protein complexes through unclear mechanisms. XIST controls the inactivation of an entire X chromosome in female placental mammals. Here we develop and integrate several orthogonal structure-interaction methods to demonstrate that XIST RNA-protein complex folds into an evolutionarily conserved modular architecture. Chimeric RNAs and clustered protein binding in fRIP and eCLIP experiments align with long-range RNA secondary structure, revealing discrete XIST domains that interact with distinct sets of effector proteins. CRISPR-Cas9-mediated permutation of the Xist A-repeat location shows that A-repeat serves as a nucleation center for multiple Xist-associated proteins and m6A modification. Thus modular architecture plays an essential role, in addition to sequence motifs, in determining the specificity of RBP binding and m6A modification. Together, this work builds a comprehensive structure-function model for the XIST RNA-protein complex, and suggests a general strategy for mechanistic studies of large ribonucleoprotein assemblies.

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Section: Discussionmentioning

confidence: 99%

Structural modularity of the XIST ribonucleoprotein complex

Guo

Wei

et al. 2020

Nat Commun

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“…The application of these methods will be instrumental in the analysis of other RNP complexes. More importantly, the discovery of compact RNP domains set the stage for focused in vitro studies of these domains through purification reconstitution, and structure analysis using physical methods (Lu and Chang, 2018).…”

Section: An Integrated Approach For Analyzing Large Rnp Complexesmentioning

confidence: 99%

Structural modularity of the XIST ribonucleoprotein complex

Guo

Wei

et al. 2019

Preprint

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words)Long noncoding RNAs are thought to regulate gene expression by organizing protein complexes through unclear mechanisms. XIST controls the inactivation of an entire X chromosome in female placental mammals. Here we develop and integrate several orthogonal structure-interaction methods to demonstrate that XIST RNA-protein complex folds into an evolutionarily conserved modular architecture. Chimeric RNAs and clustered protein binding in fRIP and eCLIP experiments align with long-range RNA secondary structure, revealing discrete XIST domains that interact with distinct sets of effector proteins. CRISPR-Cas9mediated permutation of the Xist A-repeat location shows that A-repeat serves as a nucleation center for multiple Xist-associated proteins and m 6 A modification. Thus modular architecture plays an essential role, in addition to sequence motifs, in determining the specificity of RBP binding and m 6 A modification. Together, this work builds a comprehensive structure-function model for the XIST RNA-protein complex, and suggests a general strategy for mechanistic studies of large ribonucleoprotein assemblies.

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“…Their impact on AS regulation will be further discussed by us in other chapters. The RNA structure, yet still remaining elusive, have recently been given a greater consideration as new advances have partially overcome the difficulties associated with RNA structural dynamics, lifespan, and heterogeneity in eukaryotic cells, creating a whole-transcriptome landscape of RNA structures, the RNA structurome [ 47 , 48 , 49 , 50 , 51 ].…”

Section: Introductionmentioning

confidence: 99%

Intrinsic Regulatory Role of RNA Structural Arrangement in Alternative Splicing Control

Taylor

Sobczak

2020

IJMS

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Alternative splicing is a highly sophisticated process, playing a significant role in posttranscriptional gene expression and underlying the diversity and complexity of organisms. Its regulation is multilayered, including an intrinsic role of RNA structural arrangement which undergoes time- and tissue-specific alterations. In this review, we describe the principles of RNA structural arrangement and briefly decipher its cis- and trans-acting cellular modulators which serve as crucial determinants of biological functionality of the RNA structure. Subsequently, we engage in a discussion about the RNA structure-mediated mechanisms of alternative splicing regulation. On one hand, the impairment of formation of optimal RNA structures may have critical consequences for the splicing outcome and further contribute to understanding the pathomechanism of severe disorders. On the other hand, the structural aspects of RNA became significant features taken into consideration in the endeavor of finding potential therapeutic treatments. Both aspects have been addressed by us emphasizing the importance of ongoing studies in both fields.

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The RNA Base-Pairing Problem and Base-Pairing Solutions

Cited by 32 publications

References 87 publications

Structural modularity of the XIST ribonucleoprotein complex

Structural modularity of the XIST ribonucleoprotein complex

Structural modularity of the XIST ribonucleoprotein complex

Intrinsic Regulatory Role of RNA Structural Arrangement in Alternative Splicing Control

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