The Poly(A)-Binding Protein Nuclear 1 Suppresses Alternative Cleavage and Polyadenylation Sites

Jenal, Mathias; Elkon, Ran; Loayza‐Puch, Fabricio; Haaften, Gijs van; Kühn, U.; Menzies, Fiona M.; Vrielink, Joachim A.F. Oude; Bos, Arnold J.; Drost, Jarno; Rooijers, Koos; Rubinsztein, David C.; Agami, Reuven

doi:10.1016/j.cell.2012.03.022

Cited by 304 publications

(394 citation statements)

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“…RBPs can also regulate the poly(A) tail length and control the stability and half-life of the mRNA while playing a role in poly(A) signal selection before cleavage and polyadenylation. For example, PABPN1, a nuclear poly(A)-binding protein, suppresses the use of weaker proximal signals and also stimulates PAPs to catalyze the addition of the poly(A) tail (Jenal et al 2012). Downregulation of PABPN1 has been linked to disease-specific APA patterns in heart failure, supporting the emerging roles of RBPs and APA-regulated 3′-UTR length modulation cases in diseases (Creemers et al 2016).…”

Section: Role Of Rbps In Apa Decisionsmentioning

confidence: 99%

Alternative polyadenylation and RNA-binding proteins

Erson-Bensan

2016

Journal of Molecular Endocrinology

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Our understanding of the extent of microRNA-based gene regulation has expanded in an impressive pace over the past decade. Now, we are beginning to better appreciate the role of 3′-UTR (untranslated region) cis-elements which harbor not only microRNA but also RNA-binding protein (RBP) binding sites that have significant effect on the stability and translational rate of mRNAs. To add further complexity, alternative polyadenylation (APA) emerges as a widespread mechanism to regulate gene expression by producing shorter or longer mRNA isoforms that differ in the length of their 3′-UTRs or even coding sequences. Resulting shorter mRNA isoforms generally lack cis-elements where trans-acting factors bind, and hence are differentially regulated compared with the longer isoforms. This review focuses on the RBPs involved in APA regulation and their action mechanisms on APA-generated isoforms. A better understanding of the complex interactions between APA and RBPs is promising for mechanistic and clinical implications including biomarker discovery and new therapeutic approaches.

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Section: Role Of Rbps In Apa Decisionsmentioning

confidence: 99%

Alternative polyadenylation and RNA-binding proteins

Erson-Bensan

2016

Journal of Molecular Endocrinology

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“…3B). Investigation into the mechanism of mRNA APA is still at an early stage but it likely involves general effects through bulk levels of the polyadenylation machinery (53,54), interaction of the machinery with other mRNA-processing factors (54,55), as well as more gene-specific effects through cis-regulatory elements. APA is widespread and can be controlled by both differentiation and proliferation states as 3 0 UTRs lengthen during embryonic development and shorten in the generation of induced pluripotent stem cells (51,53).…”

Section: Mrnamentioning

confidence: 99%

miRNAs in cardiac disease: Sitting duck or moving target?

2012

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SummaryEmerging findings indicate that cells can produce both micro (mi)RNAs and their messenger (m)RNA targets in multiple processing variants in a tissue-and developmental stage-selective manner. Specifically, we find that cells accumulate a greater range of functional miRNAs than hitherto expected, whereas mRNAs with alternative 3 0 untranslated regions that include varying numbers of miRNA target sites are also seen to be common. This has important implications for both our understanding of miRNA function in a given biological context and the design of successful strategies for experimental or therapeutic intervention. In this review, we relate these new phenomena to miRNAs in the heart, where they are known to play critical roles during normal function as well as in cardiac disease. IUBMBIUBMB Life, 64(11): 872-878, 2012 Keywords cardiac disease; miRNA biogenesis; miRNA-target interaction; 3 0 untranslated region; mRNA 3 0 end cleavage; polyadenylation.

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“…According to the mainstream view, functions of 3′ UTR are mediated by micro-RNA, AU-rich-element and RNA-binding proteins (RBPs) etc [6]. In general, there are more microRNA target sites in the longer 3′ UTR region, mRNA with a longer 3′ UTR displays reduced translation, whereas mRNA with shorter one has a high level of translation [4].…”

Section: Introductionmentioning

confidence: 99%

“…In other words, mRNA with paroximal ApA site or distal ApA site corresponds to short or long 3′ UTR separately, while the exons of mRNA remain unaltered. The 3′ UTR plays a significant role in post-transcriptional regulation such as regulating mRNA stability, localization, rate of protein synthesis and localization of membrane proteins [5,6]. Dysregulation of 3′ UTR has been proven to be related to a number of diseases, such as cancer, cardiovascular diseases and autoimmune diseases [7].…”

Section: Introductionmentioning

confidence: 99%

A Novel Strategy to Identify mRNA 3′ UTR and mRNA Level Difference in Crohn’s Disease

Hu¹,

Liu²,

Zhou³

et al. 2017

Chemotherapy (Los Angel)

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Background and Aims: Crohn's disease (CD) is a chronic and refractory intestinal inflammatory disease. The 3′ untranslated region (3′ UTR) of mRNA transcript can regulate its own translational process post-transciptionally, and its role in CD remains unclear. The aim of this study was to identify the critical genes influencing CD phenotype via the regulation of mRNA 3′ UTR. Methods:Isoform Structural Change Model (IsoSCM) was used to evaluate the length of 3′ UTR of the whole transciptome from a RNA-seq based online CD database. Correlations between 3′ UTR length status and mRNA level were analyzed by Spearman coefficients. Correlated genes list was overlapped with published critical CD related gene list. Univariate and multivariate analysis were performed to identify the genes associated with CD phenotype. Results:Compared with normal control, 3′ UTR of 34192 genes were shortened and 57389 were lengthened among 432784 genes in CD patients. The 3′ UTR changes of 255 genes were found significantly correlated with their mRNA level. Furthermore, 8 overlapped genes were shared by above 255 correlated genes and known CD related gene list (ABCB1, FAF1, TUT2, IL27, JAK2, LTB, NAGLU and PTPN2). The mRNA level of ABCB1 and JAK2, and shortened 3′ UTR length of JAK2 transcript were found to be correlated with deep ulcer in CD patients by univariate and multivariate analysis. Conclusions:The 3′ UTR changes of CD related genes were confirmed to be related to the phenotype of CD. Our findings may provide further insight into the epigenetic mechanisms and therapeutic strategies for CD.

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The Poly(A)-Binding Protein Nuclear 1 Suppresses Alternative Cleavage and Polyadenylation Sites

Cited by 304 publications

References 46 publications

Alternative polyadenylation and RNA-binding proteins

Alternative polyadenylation and RNA-binding proteins

miRNAs in cardiac disease: Sitting duck or moving target?

A Novel Strategy to Identify mRNA 3′ UTR and mRNA Level Difference in Crohn’s Disease

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