Regulatory feedback from nascent RNA to chromatin and transcription

Skalska, Lenka; Beltran-Nebot, Manuel; Ule, Jernej; Jenner, Richard G.

doi:10.1038/nrm.2017.12

Cited by 56 publications

(43 citation statements)

References 82 publications

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“…, recruitment of transcriptional co-activators) 10,20 . In the latter case, we might expect that MOB3B transcription would reciprocally regulate EMICERI expression.…”

mentioning

confidence: 99%

Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood

Joung

Engreitz

Konermann

et al. 2017

Nature

346

279

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The mammalian genome contains thousands of loci that transcribe long noncoding RNAs (lncRNAs)1-3, some of which are known to play critical roles in diverse cellular processes4-7. LncRNA loci can contribute to cellular regulation through a variety of mechanisms: while some encode RNAs that act non-locally (in trans)6,8, emerging evidence indicates that many lncRNA loci act locally (in cis)—for example, through functions of the lncRNA promoter, the process of lncRNA transcription, or the lncRNA transcript itself in regulating the expression of nearby genes7,9-11. Despite their potentially important roles, it remains challenging to identify functional lncRNA loci and distinguish among these and other mechanisms. To address these challenges, we developed a genome-scale CRISPR-Cas9 activation screen targeting more than 10,000 lncRNA transcriptional start sites to identify noncoding loci that influence a phenotype of interest. We found 11 novel lncRNA loci that, upon recruitment of an activator, each mediate BRAF inhibitor resistance in melanoma. We investigated potential local and non-local mechanisms at these candidate loci and found that most appear to regulate nearby genes. Detailed analysis of one candidate, termed EMICERI, revealed that its transcriptional activation results in dosage-dependent activation of four neighboring protein-coding genes, one of which confers the resistance phenotype. Our screening and characterization approach provides a CRISPR toolkit to systematically discover functions of noncoding loci and elucidate their diverse roles in gene regulation and cellular function.

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“…, recruitment of transcriptional co-activators) 10,20 . In the latter case, we might expect that MOB3B transcription would reciprocally regulate EMICERI expression.…”

mentioning

confidence: 99%

Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood

Joung

Engreitz

Konermann

et al. 2017

Nature

346

279

View full text Add to dashboard Cite

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“…Alternative splicing is a nuclear process that takes place co-transcriptionally ( Figure 2C ; Skalska et al, 2017). It has been proposed that at least in some cases, transcripts may be “poised” for splicing in the nucleus before undergoing cytoplasmic remodeling in response to extrinsic stimuli.…”

Section: Mrna Isoformsmentioning

confidence: 99%

Post-transcriptional Processing of mRNA in Neurons: The Vestiges of the RNA World Drive Transcriptome Diversity

Andreassi

Crerar

Riccio

2018

Front. Mol. Neurosci.

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Neurons are morphologically complex cells that rely on the compartmentalization of protein expression to develop and maintain their extraordinary cytoarchitecture. This formidable task is achieved, at least in part, by targeting mRNA to subcellular compartments where they are rapidly translated. mRNA transcripts are the conveyor of genetic information from DNA to the translational machinery, however, they are also endowed with additional functions linked to both the coding sequence (open reading frame, or ORF) and the flanking 5′ and 3′ untranslated regions (UTRs), that may harbor coding-independent functions. In this review, we will highlight recent evidences supporting new coding-dependent and -independent functions of mRNA and discuss how nuclear and cytoplasmic post-transcriptional modifications of mRNA contribute to localization and translation in mammalian cells with specific emphasis on neurons. We also describe recently developed techniques that can be employed to study RNA dynamics at subcellular level in eukaryotic cells in developing and regenerating neurons.

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“…It therefore seemed likely that there would be an extensive interplay between the transcriptome and chromatin-associated factors (1). Consistent with this idea, chromatin proteins were identified by mass spectrometry following UV cross-linking and purification of RNA-protein complexes in both yeast and human cells (2–4).…”

Section: Introductionmentioning

confidence: 99%

RNA Binding by Histone Methyltransferases Set1 and Set2

Sayou

Millán-Zambrano

Santos‐Rosa

et al. 2017

Molecular and Cellular Biology

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Histone methylation at H3K4 and H3K36 is commonly associated with genes actively transcribed by RNA polymerase II (RNAPII) and is catalyzed by Saccharomyces cerevisiae Set1 and Set2, respectively. Here we report that both methyltransferases can be UV cross-linked to RNA in vivo. High-throughput sequencing of the bound RNAs revealed strong Set1 enrichment near the transcription start site, whereas Set2 was distributed along pre-mRNAs. A subset of transcripts showed notably high enrichment for Set1 or Set2 binding relative to RNAPII, suggesting functional posttranscriptional interactions. In particular, Set1 was strongly bound to the SET1 mRNA, Ty1 retrotransposons, and noncoding RNAs from the ribosomal DNA (rDNA) intergenic spacers, consistent with its previously reported silencing roles. Set1 lacking RNA recognition motif 2 (RRM2) showed reduced in vivo cross-linking to RNA and reduced chromatin occupancy. In addition, levels of H3K4 trimethylation were decreased, whereas levels of dimethylation were increased. We conclude that RNA binding by Set1 contributes to both chromatin association and methyltransferase activity.

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Regulatory feedback from nascent RNA to chromatin and transcription

Cited by 56 publications

References 82 publications

Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood

Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood

Post-transcriptional Processing of mRNA in Neurons: The Vestiges of the RNA World Drive Transcriptome Diversity

RNA Binding by Histone Methyltransferases Set1 and Set2

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