Structural Modularity of the XIST Ribonucleoprotein Complex

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Dec 3

PMID 33268787

Citations 41

Authors

Zhipeng Lu

Jimmy K Guo

Yuning Wei

Diana R Dou

Brian Zarnegar

Qing Ma

Rui Li

Yang Zhao

Fan Liu

Hani Choudhry

Paul A Khavari

Howard Y Chang

Affiliations

Soon will be listed here.

Abstract

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 mA modification. Thus modular architecture plays an essential role, in addition to sequence motifs, in determining the specificity of RBP binding and mA 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.

Citing Articles

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