Proteome-wide quantitative RNA-interactome capture identifies phosphorylation sites with regulatory potential in RBM20

Vieira-Vieira, Carlos H.; Dauksaite, Vita; Sporbert, Anje; Gotthardt, Michael; Selbach, Matthias

doi:10.1016/j.molcel.2022.03.024

Cited by 18 publications

(17 citation statements)

References 98 publications

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“…For instance, stress-induced phosphorylation of HuR reduced its interaction with target mRNA in HeLa cells ( 40, 41 ). Future studies that allow combined interrogation of the interactome and the phosphoproteome may shed light on such alterations ( 42 ). Alternatively, RBPs can also compete for binding, as shown for Arid5a and ZC3H12A on the STAT3 3’UTR, and for HuR and ZFP36 (Tristetraprolin, TTP) on TNF and GM-CSF mRNA ( 20, 43, 44 ).…”

Section: Discussionmentioning

confidence: 99%

Time-dependent regulation of cytokine production by RNA binding proteins defines T cell effector function

Popović

Guislain

Engels

et al. 2021

Preprint

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SummaryEffective T cell responses against target cells require controlled production of the key pro-inflammatory cytokines IFN-γ, TNF and IL-2. Post-transcriptional events determine the magnitude and duration of cytokine production in T cells, a process that is largely regulated by RNA binding proteins (RBPs). Here we studied the identity and mode of action of RBPs interacting with cytokine mRNAs. With an RNA aptamer-based capture assay from human T cell lysates, we identified >130 RBPs interacting with the full length 3’untranslated regions of IFNG, TNF and IL2. The RBP landscape altered upon T cell activation. Furthermore, RBPs display temporal activity profiles to control cytokine production. Whereas HuR promotes early cytokine production, the peak production levels and response duration is controlled by ZFP36L1, ATXN2L and ZC3HAV1. Importantly, ZFP36L1 deletion boosts T cell responses against tumors in vivo, revealing the potential of the RBP map to identify critical modulators of T cell responses.

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Section: Discussionmentioning

confidence: 99%

Time-dependent regulation of cytokine production by RNA binding proteins defines T cell effector function

Popović

Guislain

Engels

et al. 2021

Preprint

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“…In the last decade, many research groups have successfully developed protocols based on UV cross-linking MS to not only study single RNPs but also the RBPome of different organisms and cell types. Those methods can be divided into six main groups based on their enrichment strategy of RNA–protein or RNA–peptide conjugates ( Figure 2 ): The family of RNA interactome capture (RIC) protocols comprises a variety of more specialised workflows (vRIC [ 5 ], qRIC [ 6 ], eRIC [ 7 ], cRIC [ 8 ], RBDmap [ 9 ], serIC [ 10 ]) as well as peptide cross-linking and affinity purification (pCLAP [ 11 ]), which are all based on the enrichment of poly-adenylated RNA with oligo(dT) beads. This step is highly biased towards mRNAs, but allows stringent enrichment conditions due to the very specific and strong interaction between polyA tails and the beads.…”

Section: Approaches To Study the Rbpomementioning

confidence: 99%

“…The family of RNA interactome capture (RIC) protocols comprises a variety of more specialised workflows (vRIC [ 5 ], qRIC [ 6 ], eRIC [ 7 ], cRIC [ 8 ], RBDmap [ 9 ], serIC [ 10 ]) as well as peptide cross-linking and affinity purification (pCLAP [ 11 ]), which are all based on the enrichment of poly-adenylated RNA with oligo(dT) beads. This step is highly biased towards mRNAs, but allows stringent enrichment conditions due to the very specific and strong interaction between polyA tails and the beads.…”

Section: Approaches To Study the Rbpomementioning

confidence: 99%

Protein–RNA interactions: from mass spectrometry to drug discovery

Steinmetz

Smok

Bikaki

et al. 2023

Essays in Biochemistry

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Proteins and RNAs are fundamental parts of biological systems, and their interactions affect many essential cellular processes. Therefore, it is crucial to understand at a molecular and at a systems level how proteins and RNAs form complexes and mutually affect their functions. In the present mini-review, we will first provide an overview of different mass spectrometry (MS)-based methods to study the RNA-binding proteome (RBPome), most of which are based on photochemical cross-linking. As we will show, some of these methods are also able to provide higher-resolution information about binding sites, which are important for the structural characterisation of protein–RNA interactions. In addition, classical structural biology techniques such as nuclear magnetic resonance (NMR) spectroscopy and biophysical methods such as electron paramagnetic resonance (EPR) spectroscopy and fluorescence-based methods contribute to a detailed understanding of the interactions between these two classes of biomolecules. We will discuss the relevance of such interactions in the context of the formation of membrane-less organelles (MLOs) by liquid–liquid phase separation (LLPS) processes and their emerging importance as targets for drug discovery.

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“…In the final section, this review will touch upon the effect of posttranslational modifications (PTMs) for RNP condensations. IDPs frequently contain sites PTMs such as phosphorylation, and these modifications exhibit a high preference for IDR residues (Castello et al, 2016;Vieira-Vieira et al, 2022). Arginine methylation has also been noted to play a role in RBP regulation (Gayatri and Bedford, 2014).…”

Section: Posttranslational Modificationsmentioning

confidence: 99%

Socratic Lectures 8

2023

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To date, several cardiotropic viruses have been implicated as causes of myocarditis. The most detected are parvovirus B19, and human herpes virus 6. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are the respiratory viruses that have recently triggered the unprecedented pandemic process. The involvement and impact of these viruses in viral cardiovascular disease are under study. Despite extensive research into the pathological mechanisms of viral infections of the cardiovascular system, our knowledge regarding their treatment and management is still incomplete. A condition caused by post-Co rona Virus Disease (COVID-19) myocarditis seems to have distinct inflammatory characteristics. Many kinds of arrhythmias may occur in patients with post-COVID-19 myocarditis and result in arrhythmogenic cardio-myopathy and sudden cardiac death. Sometimes arrhythmia can be the first and only symptom of myocarditis. However, compared to the other clinical presentations, arrhythmic myocarditis has been poorly described in the literature. The increased risk of arrhythmias in patients with a post-COVID-19 period is most likely a consequence of systemic inflammation and diseases, not just a direct consequence of the viral infection. A decrease in heart rate variability can contribute to electrical instability of the myocardium and the occurrence of arrhythmias. Cardiac magnetic resonance imaging and endomyocardial biopsy are the most useful tests for myocarditis. However, different from the other clinical presentations, arrhythmic myocarditis requires specific diagnostic, prognostic, and therapeutic considerations. This review aims to critically summarize the state of the art on myocarditis presenting with arrhythmias in terms of epidemiology, aetiology, diagnosis, prognosis, and treatment.

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Proteome-wide quantitative RNA-interactome capture identifies phosphorylation sites with regulatory potential in RBM20

Cited by 18 publications

References 98 publications

Time-dependent regulation of cytokine production by RNA binding proteins defines T cell effector function

Time-dependent regulation of cytokine production by RNA binding proteins defines T cell effector function

Protein–RNA interactions: from mass spectrometry to drug discovery

Socratic Lectures 8

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