Alternative mRNA transcription, processing, and translation: insights from RNA sequencing

Klerk, Eleonora de; Hoen, Peter A.C. ‘t

doi:10.1016/j.tig.2015.01.001

Cited by 277 publications

(239 citation statements)

References 148 publications

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“…Length, structure, and sequence elements in the 5′-UTRs strongly impact translation (49,50). We found that the combination of alternative TSS and splicing produces four Yy2 mRNA variants with different translation efficiencies.…”

Section: Discussionmentioning

confidence: 82%

Control of embryonic stem cell self-renewal and differentiation via coordinated alternative splicing and translation of YY2

Tahmasebi

Jafarnejad

Tam

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Translational control of gene expression plays a key role during the early phases of embryonic development. Here we describe a transcriptional regulator of mouse embryonic stem cells (mESCs), Yin-yang 2 (YY2), that is controlled by the translation inhibitors, Eukaryotic initiation factor 4E-binding proteins (4E-BPs). YY2 plays a critical role in regulating mESC functions through control of key pluripotency factors, including Octamer-binding protein 4 (Oct4) and Estrogen-related receptor-β (Esrrb). Importantly, overexpression of YY2 directs the differentiation of mESCs into cardiovascular lineages. We show that the splicing regulator Polypyrimidine tractbinding protein 1 (PTBP1) promotes the retention of an intron in the 5′-UTR of Yy2 mRNA that confers sensitivity to 4E-BP-mediated translational suppression. Thus, we conclude that YY2 is a major regulator of mESC self-renewal and lineage commitment and document a multilayer regulatory mechanism that controls its expression.mRNA translation | 4E-BPs | PTBP | embryonic stem cell | YY2

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Section: Discussionmentioning

confidence: 82%

Control of embryonic stem cell self-renewal and differentiation via coordinated alternative splicing and translation of YY2

Tahmasebi

Jafarnejad

Tam

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Alternative transcription initiation leads to the formation of transcripts with different first exon or different 5′-UTR. It has been shown that TSS selection has a critical role during development, cell differentiation and could be associated with cancer and diseases (reviewed in (121)). Genetic or epigenetic changes in the promoters as well as changes in distal elements (enhancers) could lead to a disease (121).…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that TSS selection has a critical role during development, cell differentiation and could be associated with cancer and diseases (reviewed in (121)). Genetic or epigenetic changes in the promoters as well as changes in distal elements (enhancers) could lead to a disease (121). Alternative promoters are regulated through the action of DNA methylation and histone modifications.…”

Section: Discussionmentioning

confidence: 99%

Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice

et al. 2016

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The epigenetic events imposed during germline reprogramming and affected by harmful exposure can be inherited and transferred to subsequent generations via gametes inheritance. In this study, we examine the transgenerational effects promoted by widely used herbicide atrazine (ATZ). We exposed pregnant outbred CD1 female mice and the male progeny was crossed for three generations with untreated females. We demonstrate here that exposure to ATZ affects meiosis, spermiogenesis and reduces the spermatozoa number in the third generation (F3) male mice. We suggest that changes in testis cell types originate from modified transcriptional network in undifferentiated spermatogonia. Importantly, exposure to ATZ dramatically increases the number of transcripts with novel transcription initiation sites, spliced variants and alternative polyadenylation sites. We found the global decrease in H3K4me3 occupancy in the third generation males. The regions with altered H3K4me3 occupancy in F3 ATZ-derived males correspond to altered H3K4me3 occupancy of F1 generation and 74% of changed peaks in F3 generation are associated with enhancers. The regions with altered H3K4me3 occupancy are enriched in SP family and WT1 transcription factor binding sites. Our data suggest that the embryonic exposure to ATZ affects the development and the changes induced by ATZ are transferred up to three generations.

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“…Alternative promoter and polyadenylation usage are two key mechanisms by which expression can be controlled transcriptionally or post-transcriptionally (Elkon et al 2013;de Klerk and 't Hoen 2015). Although the response of mBMDCs to LPS has been extensively characterized (Amit et al 2009;Garber et al 2012;Rabani et al 2014;Jovanovic et al 2015), the exact contribution of these two mechanisms to the transcriptional response to LPS is largely unknown.…”

Section: A Methods Specifically Designed For End-sequence Quantificationmentioning

confidence: 99%

End Sequence Analysis Toolkit (ESAT) expands the extractable information from single-cell RNA-seq data

et al. 2016

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RNA-seq protocols that focus on transcript termini are well suited for applications in which template quantity is limiting. Here we show that, when applied to end-sequencing data, analytical methods designed for global RNA-seq produce computational artifacts. To remedy this, we created the End Sequence Analysis Toolkit (ESAT). As a test, we first compared endsequencing and bulk RNA-seq using RNA from dendritic cells stimulated with lipopolysaccharide (LPS). As predicted by the telescripting model for transcriptional bursts, ESAT detected an LPS-stimulated shift to shorter 3 ′ -isoforms that was not evident by conventional computational methods. Then, droplet-based microfluidics was used to generate 1000 cDNA libraries, each from an individual pancreatic islet cell. ESAT identified nine distinct cell types, three distinct β-cell types, and a complex interplay between hormone secretion and vascularization. ESAT, then, offers a much-needed and generally applicable computational pipeline for either bulk or single-cell RNA end-sequencing.

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Alternative mRNA transcription, processing, and translation: insights from RNA sequencing

Cited by 277 publications

References 148 publications

Control of embryonic stem cell self-renewal and differentiation via coordinated alternative splicing and translation of YY2

Control of embryonic stem cell self-renewal and differentiation via coordinated alternative splicing and translation of YY2

Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice

End Sequence Analysis Toolkit (ESAT) expands the extractable information from single-cell RNA-seq data

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