A CRISPR-Cas9-based reporter system for single-cell detection of extracellular vesicle-mediated functional transfer of RNA

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Feb. 28, 2020

Abstract Extracellular vesicles (EVs) form an endogenous transport system for intercellular transfer of biological cargo, including RNA, that plays a pivotal role in physiological and pathological processes. Unfortunately, whereas effects EV-mediated RNA are abundantly studied, regulatory pathways mechanisms remain poorly defined due to lack suitable readout systems. Here, we describe highly-sensitive CRISPR-Cas9-based reporter allows direct functional study small non-coding molecules at single-cell resolution. Using this CRISPR operated stoplight exchange (CROSS-FIRE) uncover various genes involved EV subtype biogenesis play transfer. Moreover identify multiple endocytosis intracellular membrane trafficking strongly regulate delivery. Altogether, approach the elucidation level biogenesis, endocytosis, trafficking,

Language: Английский

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Recommendations for clinical interpretation of variants found in non-coding regions of the genome

Genome Medicine, Journal Year: 2022, Volume and Issue: 14(1)

Published: July 18, 2022

The majority of clinical genetic testing focuses almost exclusively on regions the genome that directly encode proteins. important role variants in non-coding penetrant disease is, however, increasingly being demonstrated, and use whole sequencing diagnostic settings is rising across a large range disorders. Despite this, there no existing guidance how current guidelines designed primarily for protein-coding should be adapted identified other genomic contexts.

Language: Английский

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Structural insights into preinitiation complex assembly on core promoters

Science, Journal Year: 2021, Volume and Issue: 372(6541)

Published: April 1, 2021

Assembling for transcription initiation Eukaryotic by RNA polymerase II (Pol II) requires the assembly of a preinitiation complex (PIC) on core promoters. The binding TATA box–binding protein (TBP) to box promoter has been thought be general rule in PIC and initiation. However, most coding genes lack box, nearly all Pol II–mediated gene TBP-containing multisubunit factor IID (TFIID). Chen et al. determined structures human TFIID-based sequential states revealed that TFIID supports distinct TATA-containing TATA-lacking finding resolves long-standing mystery how one set machinery initiates diverse Science , this issue p. eaba8490

Language: Английский

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cis-Regulatory Elements in Plant Development, Adaptation, and Evolution

Annual Review of Plant Biology, Journal Year: 2023, Volume and Issue: 74(1), P. 111 - 137

Published: Jan. 6, 2023

Regulatory elements encode the genomic blueprints that ensure proper spatiotemporal patterning of gene expression necessary for appropriate development and responses to environment. Accumulating evidence implicates changes as a major source phenotypic novelty in eukaryotes, including acute phenotypes such disease cancer mammals. Moreover, genetic epigenetic variation affecting

Language: Английский

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Compatibility rules of human enhancer and promoter sequences

Nature, Journal Year: 2022, Volume and Issue: 607(7917), P. 176 - 184

Published: May 20, 2022

Language: Английский

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