Making ends meet: coordination between RNA 3′‐end processing and transcription initiation

Andersen, Pia K.; Jensen, Torben Heick; Lykke‐Andersen, Søren

doi:10.1002/wrna.1156

Cited by 20 publications

(13 citation statements)

References 145 publications

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“…CPA factors have been detected in promoter regions (Glover-Cutter et al, 2008), where they interact with general transcription factors (Dantonel et al, 1997), transcriptional activators (Calvo and Manley, 2001; Nagaike et al, 2011) and the Pol II CTD (McCracken et al, 1997). Functional interactions between transcriptional initiation and termination have been documented (Andersen et al, 2013), for example, impaired 3′ processing can diminish initiation rates at yeast and human promoters (Mapendano et al, 2010; Zhang et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

ELAV Links Paused Pol II to Alternative Polyadenylation in the Drosophila Nervous System

et al. 2015

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SUMMARY Alternative polyadenylation (APA) has been implicated in a variety of developmental and disease processes. A particularly dramatic form of APA occurs in the developing nervous system of flies and mammals, whereby various developmental genes undergo coordinate 3′ UTR extension. In Drosophila, the RNA-binding protein ELAV inhibits RNA processing at proximal polyadenylation sites, thereby fostering the formation of exceptionally long 3′ UTRs. Here, we present evidence that paused Pol II promotes recruitment of ELAV to extended genes. Replacing promoters of extended genes with heterologous promoters blocks normal 3′ extension in the nervous system, while extension-associated promoters can induce 3′ extension in ectopic tissues expressing ELAV. Computational analyses suggest that promoter regions of extended genes tend to contain paused Pol II and associated cis-regulatory elements such as GAGA. ChIP-Seq assays identify ELAV in the promoter regions of extended genes. Our study provides evidence for a regulatory link between promoter-proximal pausing and APA.

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Section: Introductionmentioning

confidence: 99%

ELAV Links Paused Pol II to Alternative Polyadenylation in the Drosophila Nervous System

et al. 2015

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“…Since CPSF100 is associated with coiled bodies it should function in RNA biogenesis (Schul et al ., ). CPSF100 was reported to interact with transcription initiation factors that are possibly involved in transcription initiation in eukaryotic cells (Dantonel et al ., ; Wang et al ., ; Andersen et al ., ). RNA splicing subunit U2 snRNP is stably associated with CPSF100, and some splicing factors can be co‐pulled down with CPSF100 (Kyburz et al ., ; Pandya‐Jones, ).…”

Section: Discussionmentioning

confidence: 97%

Role of cleavage and polyadenylation specificity factor 100: anchoring poly(A) sites and modulating transcription termination

Lin

et al. 2017

The Plant Journal

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CPSF100 is a core component of the cleavage and polyadenylation specificity factor (CPSF) complex for 3'-end formation of mRNA, but it still has no clear functional assignment. CPSF100 was reported to play a role in RNA silencing and promote flowering in Arabidopsis. However, the molecular mechanisms underlying these phenomena are not fully understood. Our genetics analyses indicate that plants with a hypomorphic mutant of CPSF100 (esp5) show defects in embryogenesis, reduced seed production or altered root morphology. To unravel this puzzle, we employed a poly(A) tag sequencing protocol and uncovered a different poly(A) profile in esp5. This transcriptome-wide analysis revealed alternative polyadenylation of thousands of genes, most of which result in transcriptional read-through in protein-coding genes. AtCPSF100 also affects poly(A) signal recognition on the far-upstream elements; in particular it prefers less U-rich sequences. Importantly, AtCPSF100 was found to exert its functions through the change of poly(A) sites on genes encoding binding proteins, such as nucleotide-binding, RNA-binding and poly(U)-binding proteins. In addition, through its interaction with RNA Polymerase II C-terminal domain (CTD) and affecting the expression level of CTD phosphatase-like 3 (CPL3), AtCPSF100 is shown to potentially ensure transcriptional termination by dephosphorylation of Ser2 on the CTD. These data suggest a key role for CPSF100 in locating poly(A) sites and affecting transcription termination.

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“…Other mechanisms could be important, such as preformation of sub complexes [35] and local recycling. The latter has been suggested for RNA pol II through coordination between transcription and 3′ end processing [36, 37]. Another way of coordinating interactions between the transcript and specific proteins is via the RNA pol II elongation complex.…”

Section: Active Genes—optimal Nuclear Microenvironments For Transcripmentioning

confidence: 99%

Integration of mRNP formation and export

Björk

Wieslander

2017

Cell. Mol. Life Sci.

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Expression of protein-coding genes in eukaryotes relies on the coordinated action of many sophisticated molecular machineries. Transcription produces precursor mRNAs (pre-mRNAs) and the active gene provides an environment in which the pre-mRNAs are processed, folded, and assembled into RNA–protein (RNP) complexes. The dynamic pre-mRNPs incorporate the growing transcript, proteins, and the processing machineries, as well as the specific protein marks left after processing that are essential for export and the cytoplasmic fate of the mRNPs. After release from the gene, the mRNPs move by diffusion within the interchromatin compartment, making up pools of mRNPs. Here, splicing and polyadenylation can be completed and the mRNPs recruit the major export receptor NXF1. Export competent mRNPs interact with the nuclear pore complex, leading to export, concomitant with compositional and conformational changes of the mRNPs. We summarize the integrated nuclear processes involved in the formation and export of mRNPs.

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Making ends meet: coordination between RNA 3′‐end processing and transcription initiation

Cited by 20 publications

References 145 publications

ELAV Links Paused Pol II to Alternative Polyadenylation in the Drosophila Nervous System

ELAV Links Paused Pol II to Alternative Polyadenylation in the Drosophila Nervous System

Role of cleavage and polyadenylation specificity factor 100: anchoring poly(A) sites and modulating transcription termination

Integration of mRNP formation and export

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