On the function and relevance of alternative 3′‐<scp>UTRs</scp> in gene expression regulation

Pereira-Castro, Isabel; Moreira, Alexandra

doi:10.1002/wrna.1653

Cited by 42 publications

(44 citation statements)

References 234 publications

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“…Deletion of them resulted in global increase in distal PAS usage. In humans, CSTF2/CSTF64, FIP1L1, and CFIm that are homologous to yeast RNA15, FIP1, and HRP1, respectively, were reported to promote cleavage and polyadenylation at proximal PASs (Gruber & Zavolan, 2019;Pereira-Castro & Moreira, 2021). However, unlike CFIm in humans, FgRNA15 has a particularly strong impact on PAS selection in F. graminearum.…”

Section: Discussionmentioning

confidence: 99%

“…Since 3 0 -UTR affects the stability, translation rate, and subcellular localization of mRNAs (Pereira-Castro & Moreira, 2021), changes in the ratio of 3 0 -UTR isoforms in different tissues may New Phytologist (2022) 235: 674-689 www.newphytologist.com Ó 2022 The Authors New Phytologist Ó 2022 New Phytologist Foundation affect cellular functions of corresponding proteins. We found a global increase in distal PAS usage in dormant and old tissues in F. graminearum.…”

Section: Discussionmentioning

confidence: 99%

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Landscape and regulation of alternative splicing and alternative polyadenylation in a plant pathogenic fungus

Lü

Chen

et al. 2022

New Phytologist

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Summary Alternative splicing (AS) and alternative polyadenylation (APA) contribute significantly to the regulation of gene expression in higher eukaryotes. Their biological impact in filamentous fungi, however, is largely unknown. Here we combine PacBio Isoform‐Sequencing and strand‐specific RNA‐sequencing of multiple tissues and mutant characterization to reveal the landscape and regulation of AS and APA in Fusarium graminearum. We generated a transcript annotation comprising 51 617 isoforms from 17 189 genes. In total, 4997 and 11 133 genes are alternatively spliced and polyadenylated, respectively. Majority of the AS events alter coding sequences. Unexpectedly, the AS transcripts containing premature‐termination codons are not sensitive to nonsense‐mediated messenger RNA decay. Unlike in yeasts and animals, distal APA sites have strong signals, but proximal APA isoforms are highly expressed in F. graminearum. The 3′‐end processing factors FgRNA15, FgHRP1, and FgFIP1 play roles in promoting proximal APA site usage and intron splicing. A genome‐wide increase in intron inclusion and distal APA site usage and downregulation of the spliceosomal and 3′‐end processing factors were observed in older and quiescent tissues, indicating intron inclusion and 3′‐untranslated region lengthening as novel mechanisms in regulating aging and dormancy in fungi. This study provides new insights into the complexity and regulation of AS and APA in filamentous fungi.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Landscape and regulation of alternative splicing and alternative polyadenylation in a plant pathogenic fungus

Lü

Chen

et al. 2022

New Phytologist

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“…Integral approaches focusing on both pre-mRNA and miRNA regulation at the same time are scarce. For example, despite recognizing the emerging role of APA in gene expression regulation, many studies focused on the loss of miRNA binding sites within the 3'UTR 32,33 rather than consequences of intronic APA beyond shortened transcripts 34 .…”

Section: Discussionmentioning

confidence: 99%

U1 snRNP suppresses microRNA biogenesis by alternative intronic polyadenylation in melanoma

Vorlová

Blahetek

Barbieri

et al. 2022

Preprint

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Activation of intronic polyadenylation signals results in premature cleavage and polyadenylation (PCPA). The majority of mammalian microRNAs (miRNAs) are also located within intronic regions of protein-coding genes and are transcriptionally co-expressed with their host genes. Here we show that U1-dependent PCPA by an RNA surveillance mechanism termed telescripting dysregulates miRNA biogenesis in melanoma. When U1 is reduced, miR-211 levels are decreased as a direct consequence of activation of a newly identified alternative intronic polyadenylation signal located upstream of miR-211 within its host gene, the cation channel TRPM1. Various melanoma cell lines revealed decreased U1 levels and a shift from full-length to truncated TRPM1 isoforms with concomitant decreased miR-211 expression. Modulation of TRPM1 alternative polyadenylation (APA) by antisense morpholino oligonucleotides inhibits and potentially restores miR-211 expression to endogenous levels. This mechanism of intronic PCPA and its effects on miRNA biogenesis represents a previously unrecognized additional layer of gene expression regulation suitable for therapeutic modulation when dysregulated as shown for human melanoma.

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“…In any case, alterations in the mechanisms regulating 3′UTR length would result in widespread deregulations of gene expression that could eventually lead to diseases, likely linked to the loss of specific miRNA binding sites ( Table 1 ) [ 83 , 84 ]. While long 3′UTRs have been mostly detected in quiescent stem cells, differentiated cells, or early in development, shortened 3′UTRs have been mostly described in quickly cycling cells such as proliferative stem/progenitor cells or tumour cells [ 85 , 86 , 87 ]. Thus, shortened 3′UTRs have been reported in proliferation-related transcripts in triple negative breast cancers [ 88 ], non-small cell lung cancer [ 89 ], glioblastoma [ 90 ], esophageal carcinoma [ 91 ], multiple myeloma [ 92 ], colorectal cancer [ 93 ] cardiac hypertrophy [ 94 ], etc.…”

Section: Regulation Of 3′utr Length By Alternative Polyadenylation or Alternative Splicingmentioning

confidence: 99%

Dynamic Variations of 3′UTR Length Reprogram the mRNA Regulatory Landscape

2021

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This paper concerns 3′-untranslated regions (3′UTRs) of mRNAs, which are non-coding regulatory platforms that control stability, fate and the correct spatiotemporal translation of mRNAs. Many mRNAs have polymorphic 3′UTR regions. Controlling 3′UTR length and sequence facilitates the regulation of the accessibility of functional effectors (RNA binding proteins, miRNAs or other ncRNAs) to 3′UTR functional boxes and motifs and the establishment of different regulatory landscapes for mRNA function. In this context, shortening of 3′UTRs would loosen miRNA or protein-based mechanisms of mRNA degradation, while 3′UTR lengthening would strengthen accessibility to these effectors. Alterations in the mechanisms regulating 3′UTR length would result in widespread deregulation of gene expression that could eventually lead to diseases likely linked to the loss (or acquisition) of specific miRNA binding sites. Here, we will review the mechanisms that control 3′UTR length dynamics and their alterations in human disorders. We will discuss, from a mechanistic point of view centered on the molecular machineries involved, the generation of 3′UTR variability by the use of alternative polyadenylation and cleavage sites, of mutually exclusive terminal alternative exons (exon skipping) as well as by the process of exonization of Alu cassettes to generate new 3′UTRs with differential functional features.

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On the function and relevance of alternative 3′‐UTRs in gene expression regulation

Cited by 42 publications

References 234 publications

Landscape and regulation of alternative splicing and alternative polyadenylation in a plant pathogenic fungus

Landscape and regulation of alternative splicing and alternative polyadenylation in a plant pathogenic fungus

U1 snRNP suppresses microRNA biogenesis by alternative intronic polyadenylation in melanoma

Dynamic Variations of 3′UTR Length Reprogram the mRNA Regulatory Landscape

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