The nexus between RNA-binding proteins and their effectors

He, Shiyang; Valkov, Eugene; Cheloufi, Sihem; Murn, Jernej

doi:10.1038/s41576-022-00550-0

Cited by 44 publications

(33 citation statements)

References 197 publications

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“…The subunits of CCR4-NOT with which UNK interacts via SLiMs are also known to be targeted by divergent SLiMs of other RBPs and non-RBPs, indicating an independent but convergent evolution of IDR-embedded SLiMs of UNK 2,9,33,[49][50][51][52][53] . However, unlike the multivalent interface between the UNK homodimer and CCR4-NOT described here, only one or at most two contacts have been experimentally validated between any other protein and CCR4-NOT, although more numerous contacts are suspected to exist 9,39 .…”

Section: Discussionmentioning

confidence: 99%

“…RNA processing is executed by a diverse set of effector proteins and protein complexes that specialize in facilitating a particular molecular event during the lifetime of an RNA. Although several effectors may act on RNA with little specificity, effector activities are often regulated to affect certain transcripts or their parts more than others 1,2 . Specificity in RNA processing is essential for a range of key cellular functions, including cellular differentiation, timely responses to immune signaling, or synaptic plasticity [3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

“…An emerging theme is that RBP–effector interactions are often mediated by a short linear motif (SLiM) embedded within RBP’s intrinsically disordered region (IDR), which supports direct contact with a structured domain of an effector protein 2 . A few essential residues in these SLiMs provide specificity in transient interactions 15 .…”

Section: Introductionmentioning

confidence: 99%

“…Specificity in RNA processing is essential for a range of key cellular functions, including cellular differentiation, timely responses to immune signaling, or synaptic plasticity [3][4][5] . Critical to regulated RNA processing are RNAbinding proteins (RBPs) that can, by interacting with both the RNA and the effector, divert effector activity towards specific, RBP-targeted transcripts 1,2,6 .…”

Section: Introductionmentioning

confidence: 99%

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A paradigm for regulation at the effector interface with RNA-binding proteins

Shah,

He,

Turner

et al. 2023

Preprint

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RNA-binding proteins (RBPs) are key regulators of gene expression, but how RBPs convey regulatory instructions to the core effectors of RNA processing is unclear. We address this problem by dissecting the effector interface responsible for regulation by a developmentally essential RBP. We show that the sequence-specific RBP Unkempt, in addition to its RNA-binding domain, contains an extensive intrinsically disordered region (IDR) and a dimerization domain, all of which distinctly contribute to Unkempt's function. Within IDR, we identify an array of linear motifs that support direct contact with two central effectors, the CCR4-NOT complex and PABPC. The spatial arrangement, dual-purpose motifs, and obligate homodimerization allow for high-avidity effector interactions that are mandatory for the accuracy of RNA targeting, translational repression, and control of cell morphology by Unkempt. Our study establishes the molecular assembly and functional principles of an RBP-effector interface, with general implications for the evolution and function of RBP-operated regulatory networks.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A paradigm for regulation at the effector interface with RNA-binding proteins

Shah,

He,

Turner

et al. 2023

Preprint

Self Cite

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“…Approximately 1,900 and 1,400 proteins are cataloged as RBPs in Homo sapiens and Mus musculus , respectively, or more in other new datasets ( Hentze et al, 2018 ). In principle, RBPs could bind to a specific sequence and/or structural motif in the RNA via their canonical or non-conventional RNA-binding domains ( Hentze et al, 2018 ) and sequentially recruit different commitment proteins or complex, such as RNA degradation machineries to regulate the fate of bound RNAs ( He et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Control of RNA degradation in cell fate decision

Deng

Wang²,

Xiong

et al. 2023

Front. Cell Dev. Biol.

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Cell fate is shaped by a unique gene expression program, which reflects the concerted action of multilayered precise regulation. Substantial research attention has been paid to the contribution of RNA biogenesis to cell fate decisions. However, increasing evidence shows that RNA degradation, well known for its function in RNA processing and the surveillance of aberrant transcripts, is broadly engaged in cell fate decisions, such as maternal-to-zygotic transition (MZT), stem cell differentiation, or somatic cell reprogramming. In this review, we first look at the diverse RNA degradation pathways in the cytoplasm and nucleus. Then, we summarize how selective transcript clearance is regulated and integrated into the gene expression regulation network for the establishment, maintenance, and exit from a special cellular state.

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RBMS1 Coordinates with the m⁶A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation

Sun,

Chen,

Sun

et al. 2024

Advanced Science

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Metastasis is the leading cause for the high mortality of lung cancer, however, effective anti‐metastatic drugs are still limited. Here it is reported that the RNA‐binding protein RBMS1 is positively associated with increased lymph node metastasis in non‐small cell lung cancer (NSCLC). Depletion of RBMS1 suppresses cancer cell migration and invasion in vitro and inhibits cancer cell metastasis in vivo. Mechanistically, RBMS1 interacts with YTHDF1 to promote the translation of S100P, thereby accelerating NSCLC cell metastasis. The RRM2 motif of RBMS1 and the YTH domain of YTHDF1 are required for the binding of RBMS1 and YTHDF1. RBMS1 ablation inhibits the translation of S100P and suppresses tumor metastasis. Targeting RBMS1 with NTP, a small molecular chemical inhibitor of RBMS1, attenuates tumor metastasis in a mouse lung metastasis model. Correlation studies in lung cancer patients further validate the clinical relevance of the findings. Collectively, the study provides insight into the molecular mechanism by which RBMS1 promotes NSCLC metastasis and offers a therapeutic strategy for metastatic NSCLC.

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The nexus between RNA-binding proteins and their effectors

Cited by 44 publications

References 197 publications

A paradigm for regulation at the effector interface with RNA-binding proteins

A paradigm for regulation at the effector interface with RNA-binding proteins

Control of RNA degradation in cell fate decision

RBMS1 Coordinates with the m⁶A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation

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The nexus between RNA-binding proteins and their effectors

Cited by 44 publications

References 197 publications

A paradigm for regulation at the effector interface with RNA-binding proteins

A paradigm for regulation at the effector interface with RNA-binding proteins

Control of RNA degradation in cell fate decision

RBMS1 Coordinates with the m6A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation

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Product

Resources

About

RBMS1 Coordinates with the m⁶A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation