Toward a Systematic Understanding of mRNA 3' Untranslated Regions

Zhao, Wenxue; Blagev, Denitza; Pollack, Joshua L.; Erle, David J.

doi:10.1513/pats.201007-054ms

Cited by 24 publications

(19 citation statements)

References 45 publications

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“…Together, these pre-mRNA splice variants are expected to reduce activity of the isocitrate dehydrogenase complex. Sdha exhibited a small but significant increase in 39 UTR levels in recruited AMs compared to resident AMs, which we speculate could modify Sdha mRNA mRNA localization, mRNA stability, or translation (Zhao et al 2011;Matoulkova et al 2012;Mayr 2019).…”

Section: Pre-mrna Splicing Is Altered In Alveolar Macrophages During mentioning

confidence: 84%

Inflammation-Induced Alternative Pre-mRNA Splicing in Mouse Alveolar Macrophages

Janssen

Danhorn²,

Harris

et al. 2020

G3 Genes|Genomes|Genetics

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Alveolar macrophages serve as central orchestrators of inflammatory responses in the lungs, both initiating their onset and promoting their resolution. However, the mechanisms that program macrophages for these dynamic responses are not fully understood. Over 95% of all mammalian genes undergo alternative pre-mRNA splicing. While alternative splicing has been shown to regulate inflammatory responses in macrophages in vitro, it has not been investigated on a genome-wide scale in vivo. Here we used RNAseq to investigate alternative pre-mRNA splicing in alveolar macrophages isolated from lipopolysaccharide (LPS)-treated mice during the peak of inflammation and during its resolution. We found that lung inflammation induced substantial alternative pre-mRNA splicing in alveolar macrophages. The number of changes in isoform usage was greatest at the peak of inflammation and involved multiple classes of alternative pre-mRNA splicing events. Comparative pathway analysis of inflammation-induced changes in alternative pre-mRNA splicing and differential gene expression revealed overlap of pathways enriched for immune responses such as chemokine signaling and cellular metabolism. Moreover, alternative pre-mRNA splicing of genes in metabolic pathways differed in tissue resident vs. recruited (blood monocyte-derived) alveolar macrophages and corresponded to changes in core metabolism, including a switch to Warburg-like metabolism in recruited macrophages with increased glycolysis and decreased flux through the tricarboxylic acid cycle.

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Section: Pre-mrna Splicing Is Altered In Alveolar Macrophages During mentioning

confidence: 84%

Inflammation-Induced Alternative Pre-mRNA Splicing in Mouse Alveolar Macrophages

Janssen

Danhorn²,

Harris

et al. 2020

G3 Genes|Genomes|Genetics

View full text Add to dashboard Cite

show abstract

“…Furthermore, many transcript isoforms differ not only in coding exons but also (some exclusively) in their 5′ and 3′ untranslated regions. These changes can have dramatic effects on mRNA stability and translation efficiency (241,242).…”

Section: Alternative Splicingmentioning

confidence: 99%

Interferon-Stimulated Genes: A Complex Web of Host Defenses

Schneider

Dittmann

Rice

2014

Annu. Rev. Immunol.

2,564

2,503

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Interferon-stimulated gene (ISG) products take on a number of diverse roles. Collectively, they are highly effective at resisting and controlling pathogens. In this review, we begin by introducing interferon (IFN) and the JAK-STAT signaling pathway to highlight features that impact ISG production. Next, we describe ways in which ISGs both enhance innate pathogen-sensing capabilities and negatively regulate signaling through the JAK-STAT pathway. Several ISGs that directly inhibit virus infection are described with an emphasis on those that impact early and late stages of the virus life cycle. Finally, we describe ongoing efforts to identify and characterize antiviral ISGs, and we provide a forward-looking perspective on the ISG landscape.

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“…Significant efforts have focused on the role(s) of 3= untranslated region (3=UTR) determinants in these processes. Regulatory roles of 3=UTRs have been defined in nuclear RNA processing and mRNA transport as well as in the localization, translation, and decay of cytoplasmic mRNAs (4,5).…”

mentioning

confidence: 99%

αCP Poly(C) Binding Proteins Act as Global Regulators of Alternative Polyadenylation

Wan

Vishnu

et al. 2013

Molecular and Cellular Biology

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eWe have previously demonstrated that the KH-domain protein ␣CP binds to a 3= untranslated region (3=UTR) C-rich motif of the nascent human alpha-globin (h␣-globin) transcript and enhances the efficiency of 3= processing. Here we assess the genomewide impact of ␣CP RNA-protein (RNP) complexes on 3= processing with a specific focus on its role in alternative polyadenylation (APA) site utilization. The major isoforms of ␣CP were acutely depleted from a human hematopoietic cell line, and the impact on mRNA representation and poly(A) site utilization was determined by direct RNA sequencing (DRS). Bioinformatic analysis revealed 357 significant alterations in poly(A) site utilization that could be specifically linked to the ␣CP depletion. These APA events correlated strongly with the presence of C-rich sequences in close proximity to the impacted poly(A) addition sites. The most significant linkage was the presence of a C-rich motif within a window 30 to 40 bases 5= to poly(A) signals (AAU AAA) that were repressed upon ␣CP depletion. This linkage is consistent with a general role for ␣CPs as enhancers of 3= processing. These findings predict a role for ␣CPs in posttranscriptional control pathways that can alter the coding potential and/or levels of expression of subsets of mRNAs in the mammalian transcriptome.

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Toward a Systematic Understanding of mRNA 3' Untranslated Regions

Cited by 24 publications

References 45 publications

Inflammation-Induced Alternative Pre-mRNA Splicing in Mouse Alveolar Macrophages

Inflammation-Induced Alternative Pre-mRNA Splicing in Mouse Alveolar Macrophages

Interferon-Stimulated Genes: A Complex Web of Host Defenses

αCP Poly(C) Binding Proteins Act as Global Regulators of Alternative Polyadenylation

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