Terminal nucleotidyl transferases (TENTs) in mammalian RNA metabolism

Warkocki, Zbigniew; Liudkovska, Vladyslava; Gewartowska, Olga; Mroczek, Seweryn; Dziembowski, Andrzej

doi:10.1098/rstb.2018.0162

Cited by 57 publications

(57 citation statements)

References 215 publications

(390 reference statements)

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“…Recently, we presented the first experimental data for a new family of non-canonical cytoplasmic poly(A) polymerases TENT5 (formerly FAM46) (Warkocki et al, 2018). One of the members, TENT5C, was shown to be a specific growth suppressor in multiple myeloma cells (Mroczek et al, 2017; Zhu et al, 2017) and is the only TENT5 family member expressed at significant levels in B lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

B cell humoral response and differentiation is regulated by the non-canonical poly(A) polymerase TENT5C

Bilska

Kusio-Kobiałka

Krawczyk

et al. 2019

Preprint

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31TENT5C is a non-canonical cytoplasmic poly(A) polymerase (ncPAP) upregulated in 32 activated B cells and suppressing their proliferation. Herein we measured the global distribution of 33 poly(A) tail lengths in responsive B cells using a modified Nanopore direct RNA-sequencing 34 approach and revealed that TENT5C polyadenylates immunoglobulin mRNAs regulating their 35 steady-state levels. Consequently, TENT5C deficient B cells secrete less antibodies and KO mice 36 have diminished gamma globulin concentrations despite the increased number of CD138 high plasma 37 cells as a consequence of accelerated differentiation. TENT5C is explicitly upregulated in 38 differentiating plasma cells by innate signaling. Importantly, TENT5C deficiency in B lymphocytes 39 impairs the capacity of the secretory pathway through the reduction of ER volume and 40 downregulation of unfolded protein response. 41 Our findings define the role of the TENT5C enzyme in B cell physiology and discover the 42 first ncPAP engaged in the regulation of immunoglobulin mRNA poly(A) tails, thus serving as a 43 regulator of humoral immunity. 44 45 46 Introduction 47 Development of an adaptive humoral immune response requires activation of resting B cells 48 following antigen recognition. This process is associated with structural and functional changes 49 leading to the generation of high-affinity memory B cells and antibody-secreting plasma cells (ASC). 50 Extensive B cell differentiation is characterized by the clonal expansion, somatic hypermutation 51 leading to affinity maturation, isotype switching, and formation of ASC or memory cells. At a cellular 52 level, this process involves the reorganization of the rough endoplasmic reticulum (ER) and Golgi 53 compartments to promote immunoglobulin synthesis, assembly and secretion (Lynes and Simmen, 54 2011; Wiest et al., 1990). These global physiological changes occurring during B cell differentiation 55 and activation are linked to broad changes in the transcriptomic profile which is controlled by the 56 coordinated action of regulatory networks of transcriptional factors such as NF-kB, BCL6, IRF4, and 57

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Section: Discussionmentioning

confidence: 99%

B cell humoral response and differentiation is regulated by the non-canonical poly(A) polymerase TENT5C

Bilska

Kusio-Kobiałka

Krawczyk

et al. 2019

Preprint

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“…They belong to a group of terminal nucleotidyltrasferases (TENT), sometimes also referred to as non-canonical poly(A)-polymerases (ncPAPs). For a detailed review of the biology, biochemistry and terminology of TUTases and ncPAPs, see articles by de Almeida et al [8] and Warkocki et al [9]. The 3 0 terminal non-templated oligo(U) extensions have been detected in diverse eukaryotes in a wide range of transcripts produced by all three nuclear RNA polymerases, respectively (summarized in table 1).…”

Section: Recognition Of Rna Uridylation As An Essential Posttranscripmentioning

confidence: 99%

“…Based on the nucleotide specificity (ATP or UTP), they can be classified as either PAPs or TUTases. For more details, see article by Warkocki et al [9]. Most of the ncPAPs display a distributive terminal transferase activity, which can be significantly enhanced by their association with either RNA-binding proteins or other small molecule cofactors [52][53][54][55].…”

Section: The Factors Involved In Uridylation Pathways (A) Terminal Urmentioning

confidence: 99%

The role of 3′ end uridylation in RNA metabolism and cellular physiology

Zigáčková¹,

Vaňáčová²

2018

Phil. Trans. R. Soc. B

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One contribution of 11 to a theme issue '5 0 and 3 0 modifications controlling RNA degradation'.Most eukaryotic RNAs are posttranscriptionally modified. The majority of modifications promote RNA maturation, others may regulate function and stability. The 3 0 terminal non-templated oligouridylation is a widespread modification affecting many cellular RNAs at some stage of their life cycle. It has diverse roles in RNA metabolism. The most prevalent is the regulation of stability and quality control. On the cellular and organismal level, it plays a critical role in a number of pathways, such as cell cycle regulation, cell death, development or viral infection. Defects in uridylation have been linked to several diseases. This review summarizes the current knowledge about the role of the 3 0 terminal oligo(U)-tailing in biology of various RNAs in eukaryotes and describes key factors involved in these pathways.This article is part of the theme issue '5 0 and 3 0 modifications controlling RNA degradation'.

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“…Our approach builds on RNA Tagging, used initially to identify RNAs that bind cognate proteins in vivo 26 . In those studies, the RBP to be tested was linked to an enzyme that adds uridine residues (termed a "PUP," "TUTase" 27 , or TENT 28 ) to the RNA. When the chimeric protein bound an RNA molecule in vivo, the end was "tagged" with uridine residues.…”

Section: Introductionmentioning

confidence: 99%

Records of RNA localization through covalent tagging

Medina-Munoz

Lapointe

Porter

et al. 2019

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RNA movements and localization pervade biology, from embryonic development to disease. To identify RNAs at specific subcellular locations, we anchored a uridine-adding enzyme at those sites, which then marked RNAs in its vicinity with 3' terminal uridines. RNAs were tagged independent of their translation status, and included not only mRNAs, but also ncRNAs and ncRNA processing intermediates. A battery of RNAs, including the stress sensor, IRE1, were tagged at both ER and mitochondria, and reveal RNAs whose dual localization is conserved from yeast to human cells.

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Terminal nucleotidyl transferases (TENTs) in mammalian RNA metabolism

Cited by 57 publications

References 215 publications

B cell humoral response and differentiation is regulated by the non-canonical poly(A) polymerase TENT5C

B cell humoral response and differentiation is regulated by the non-canonical poly(A) polymerase TENT5C

The role of 3′ end uridylation in RNA metabolism and cellular physiology

Records of RNA localization through covalent tagging

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