HnRNP A1/A2 Proteins Assemble onto 7SK snRNA via Context Dependent Interactions

Luo, Le; Chiu, Liang‐Yuan; Sugarman, Andrew; Gupta, Payal; Rouskin, Silvi; Tolbert, Blanton S.

doi:10.1016/j.jmb.2021.166885

Cited by 22 publications

(30 citation statements)

References 51 publications

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“…4C, S9B). Prior studies have also observed that mutations in the SL2ext region induce global remodeling of 7SK structure (Brogie and Price, 2017; Luo et al, 2021), although the mechanistic basis was not resolved. Thus, even though SL2ext shows intermediate stability, this region is critical to 7SK A:B switching.…”

Section: Resultsmentioning

confidence: 99%

“…Several studies have observed that HEXIM/P-TEFb release coincides with conformational changes in the SL1 aptamer (Krueger et al, 2010; Brogie and Price, 2017). Binding of hnRNPs has also been observed to induce conformational changes in the 7SK central domain (Luo et al, 2021). However, the relationship between these conformational changes and their role in P-TEFb release remained unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The 7SK RNA is highly structured (Wassarman and Steitz, 1991) and several studies support the model that P-TEFb binding and release involves remodeling of 7SK RNA structure (Krueger et al, 2010; Brogie and Price, 2017), or that the 7SK RNA exists in distinct conformations depending which proteins are bound (Krueger et al, 2010; Flynn et al, 2016; Brogie and Price, 2017). Multiple models for the 7SK RNA structure have been proposed (Wassarman and Steitz, 1991; Marz et al, 2009; Brogie and Price, 2017; Luo et al, 2021), but the accuracy of these models, whether they represent distinct co-existing states, and how these states might differentially modulate function remains unknown. To date, 7SK structure has primarily been studied using ensemble-average chemical probing approaches that are poorly suited for identifying coexisting RNA conformations or resolving in-cell structural dynamics.…”

Section: Introductionmentioning

confidence: 99%

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Large-scale allosteric switch in the 7SK RNA regulates transcription in response to growth and stress

Olson

Turner²,

Arney³

et al. 2021

Preprint

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7SK is a highly conserved non-coding RNA that regulates eukaryotic transcription by sequestering positive transcription elongation factor b (P-TEFb). 7SK regulatory function likely entails changes in RNA structure, but characterizing dynamic RNA-protein complexes in cells has remained an unsolved challenge. We describe a new chemical probing strategy (DANCE-MaP) that uses maximum likelihood deconvolution and probabilistic read assignment to define simultaneously (i) per-nucleotide reactivity profiles, (ii) direct base pairing interactions, and (iii) tertiary and higher-order interactions for each conformation of multi-state RNA structural ensembles, all from a single experiment. We show that human 7SK RNA, despite significant heterogeneity, intrinsically codes for a large-scale structural switch that couples dissolution of the P-TEFb binding site to structural remodeling at distal release factor binding sites. The 7SK structural equilibrium is regulated by cell type, shifts dynamically in response to cell growth and stress, and can be exogenously targeted to modulate transcription in cells. Our data support that the 7SK structural ensemble functions as an integrator of diverse cellular signals to control transcription elongation in environment and cell specific ways, and establishes DANCE-MaP as a powerful strategy for comprehensively defining RNA structure and dynamics in cells.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Large-scale allosteric switch in the 7SK RNA regulates transcription in response to growth and stress

Olson

Turner²,

Arney³

et al. 2021

Preprint

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“…[22,23] These hnRNPs use stem loop 3 of 7SK as interaction site and thus differ from P-TEFb, which associates with stem-loop 1 via HEXIM1. [22,25,27,28] Importantly, binding of hnRNPs and P-TEFb to 7SK is mutually exclusive and the balance between these 7SK subcomplexes is determined by the transcriptional activity of a cell (Figure 1A). [22,23] 7SK is highly expressed in the nervous system during development and into adulthood.…”

Section: Sk Provides Regulatory Support For Axon Growth During Neuron Developmentmentioning

confidence: 99%

“…[ 22,23 ] These hnRNPs use stem loop 3 of 7SK as interaction site and thus differ from P‐TEFb, which associates with stem‐loop 1 via HEXIM1. [ 22,25,27,28 ]…”

Section: Sk Provides Regulatory Support For Axon Growth During Neuron Developmentmentioning

confidence: 99%

Keeping the balance: The noncoding RNA 7SK as a master regulator for neuron development and function

Briese

Sendtner

2021

BioEssays

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The noncoding RNA 7SK is a critical regulator of transcription by adjusting the activity of the kinase complex P-TEFb. Release of P-TEFb from 7SK stimulates transcription at many genes by promoting productive elongation. Conversely, P-TEFb sequestration by 7SK inhibits transcription. Recent studies have shown that 7SK functions are particularly important for neuron development and maintenance and it can thus be hypothesized that 7SK is at the center of many signaling pathways contributing to neuron function. 7SK activates neuronal gene expression programs that are key for terminal differentiation of neurons. Proteomics studies revealed a complex protein interactome of 7SK that includes several RNA-binding proteins. Some of these novel 7SK subcomplexes exert non-canonical cytosolic functions in neurons by regulating axonal mRNA transport and fine-tuning spliceosome production in response to transcription alterations. Thus, a picture emerges according to which 7SK acts as a multi-functional RNA scaffold that is integral for neuron homeostasis. K E Y W O R D S7SK, heterogeneous nuclear ribonucleoprotein (hnRNP), positive transcription elongation factor b (P-TEFb), survival motor neuron (SMN) This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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C-terminal determinants for RNA binding motif 7 protein stability and RNA recognition

Sobeh

Eichhorn²

2023

Biophysical Chemistry

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HnRNP A1/A2 Proteins Assemble onto 7SK snRNA via Context Dependent Interactions

Cited by 22 publications

References 51 publications

Large-scale allosteric switch in the 7SK RNA regulates transcription in response to growth and stress

Large-scale allosteric switch in the 7SK RNA regulates transcription in response to growth and stress

Keeping the balance: The noncoding RNA 7SK as a master regulator for neuron development and function

C-terminal determinants for RNA binding motif 7 protein stability and RNA recognition

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