Introns in UTRs: Why we should stop ignoring them

Bicknell, Alicia A.; Cenik, Can; Chua, Hon Nian; Roth, Frederick P.; Moore, Melissa J.

doi:10.1002/bies.201200073

Cited by 111 publications

(103 citation statements)

References 85 publications

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“…Viewed in this context, our observed clustering of DMMs around untranslated regions (UTRs) and exons is at least consistent with salt-induced DMMs mediating a functional response to the stress. Others have shown that a high frequency of salt-induced DMMs in gene extremities (towards 5 UTR and 3 UTR) can influence gene regulation through 5 UTR' and 3 UTR' closed-loop regulation systems which generate inactive transcripts [70,71], or through independent gene regulation by each UTR type [72]. Karan et al [25] similarly observed that salt-induced DNA methylation changes generally occur in exon and UTR regions and could affect diverse biological functions in plants.…”

Section: Salt-induced Changes In Dna Methylation May Influence Gene Rmentioning

confidence: 87%

Salt Stress Induces Non-CG Methylation in Coding Regions of Barley Seedlings (Hordeum vulgare)

et al. 2018

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Salinity can negatively impact crop growth and yield. Changes in DNA methylation are known to occur when plants are challenged by stress and have been associated with the regulation of stress-response genes. However, the role of DNA-methylation in moderating gene expression in response to salt stress has been relatively poorly studied among crops such as barley. Here, we assessed the extent of salt-induced alterations of DNA methylation in barley and their putative role in perturbed gene expression. Using Next Generation Sequencing, we screened the leaf and root methylomes of five divergent barley varieties grown under control and three salt concentrations, to seek genotype independent salt-induced changes in DNA methylation. Salt stress caused increased methylation in leaves but diminished methylation in roots with a higher number of changes in leaves than in roots, indicating that salt induced changes to global methylation are organ specific. Differentially Methylated Markers (DMMs) were mostly located in close proximity to repeat elements, but also in 1094 genes, of which many possessed gene ontology (GO) terms associated with plant responses to stress. Identified markers have potential value as sentinels of salt stress and provide a starting point to allow understanding of the functional role of DNA methylation in facilitating barley's response to this stressor.

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Section: Salt-induced Changes In Dna Methylation May Influence Gene Rmentioning

confidence: 87%

Salt Stress Induces Non-CG Methylation in Coding Regions of Barley Seedlings (Hordeum vulgare)

et al. 2018

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“…Our data suggest that as many as 10% of all S. pombe genes contain an intron within their 5′ or 3′ UTRs. Although such introns have often been ignored, recent work strongly argues in favor of a role for these introns in regulating gene expression (36).…”

Section: Lariat Sequencing Identifies Over 200 Previously Uncharactermentioning

confidence: 99%

Lariat sequencing in a unicellular yeast identifies regulated alternative splicing of exons that are evolutionarily conserved with humans

Awan

Manfredo

Pleiss

2013

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

113

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Alternative splicing is a potent regulator of gene expression that vastly increases proteomic diversity in multicellular eukaryotes and is associated with organismal complexity. Although alternative splicing is widespread in vertebrates, little is known about the evolutionary origins of this process, in part because of the absence of phylogenetically conserved events that cross major eukaryotic clades. Here we describe a lariat-sequencing approach, which offers high sensitivity for detecting splicing events, and its application to the unicellular fungus, Schizosaccharomyces pombe, an organism that shares many of the hallmarks of alternative splicing in mammalian systems but for which no previous examples of exon-skipping had been demonstrated. Over 200 previously unannotated splicing events were identified, including examples of regulated alternative splicing. Remarkably, an evolutionary analysis of four of the exons identified here as subject to skipping in S. pombe reveals high sequence conservation and perfect length conservation with their homologs in scores of plants, animals, and fungi. Moreover, alternative splicing of two of these exons have been documented in multiple vertebrate organisms, making these the first demonstrations of identical alternative-splicing patterns in species that are separated by over 1 billion y of evolution.pre-mRNA splicing | post-transcriptional gene regulation | phylogeny T he protein coding regions of eukaryotic genes are typically interrupted by noncoding introns that must be removed to produce a translatable mRNA. The removal of introns, catalyzed by the spliceosome, offers a powerful opportunity for an organism to regulate gene expression. In mammals, where individual genes are often interrupted by multiple introns, it is now abundantly clear that the process of intron removal provides a critical regulatory control point for both qualitative and quantitative aspects of gene expression (1). By changing the identity of the exons that are included within the final mRNA, the process of alternative splicing plays a critical role in expanding the diversity of proteins that can be synthesized within a cell (2). Moreover, alternative splicing can direct the production of isoforms of genes that are directly targeted to cellular decay pathways, providing a mechanism to quantitatively regulate gene expression (3, 4).In mammalian organisms the predominant form of alternative splicing is exon skipping, wherein different combinations of exons are included in the final transcript. In contrast, exon skipping is far less prevalent in simpler eukaryotes (5, 6); however, recent studies suggest that splicing in the last eukaryotic common ancestor was similar in many respects to splicing in vertebrates, in so much as it was intron-dense (7-9), had degenerate splice site sequences (10), and likely had many of the proteins involved in alternative splicing (11,12). Intron density correlates positively with the prevalence of alternative splicing across the eukaryotic kingdoms (13), and thus it has...

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“…For that reason, some investigators took measures to stay clear of transcripts that are located in a certain proximity to annotated protein-coding genes (Managadze et al 2013). Nevertheless, splicing does occur in 3 0 -UTRs as well (Bicknell et al 2012;Camacho-Vanegas et al 2012;Zhernakova et al 2013) and, hence, the corresponding exons could map to corresponding protein-coding genes at a much greater distance to the ORFs. Furthermore, apart from spurious initiation of transcription anywhere in the genome, a certain level of readthrough into gene distal regions could account for a significant portion of these long RNA candidates (Finta and Zaphiropoulos 2000;Akiva et al 2006;Parra et al 2006;Richard and Manley 2009).…”

Section: Did Rna Enter Bubble Territory?mentioning

confidence: 99%

The Persistent Contributions of RNA to Eukaryotic Gen(om)e Architecture and Cellular Function

Brosius

2014

Cold Spring Harbor Perspectives in Biology

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Introns in UTRs: Why we should stop ignoring them

Cited by 111 publications

References 85 publications

Salt Stress Induces Non-CG Methylation in Coding Regions of Barley Seedlings (Hordeum vulgare)

Salt Stress Induces Non-CG Methylation in Coding Regions of Barley Seedlings (Hordeum vulgare)

Lariat sequencing in a unicellular yeast identifies regulated alternative splicing of exons that are evolutionarily conserved with humans

The Persistent Contributions of RNA to Eukaryotic Gen(om)e Architecture and Cellular Function

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