Publications by authors named "Ana Hidalgo-Sastre"

14 Publications

  • Page 1 of 1

Inhibition of Wnt signalling by Notch via two distinct mechanisms.

Sci Rep 2021 Apr 27;11(1):9096. Epub 2021 Apr 27.

Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.

Notch and Wnt are two essential signalling pathways that help to shape animals during development and to sustain adult tissue homeostasis. Although they are often active at the same time within a tissue, they typically have opposing effects on cell fate decisions. In fact, crosstalk between the two pathways is important in generating the great diversity of cell types that we find in metazoans. Several different mechanisms have been proposed that allow Notch to limit Wnt signalling, driving a Notch-ON/Wnt-OFF state. Here we explore these different mechanisms in human cells and demonstrate two distinct mechanisms by which Notch itself, can limit the transcriptional activity of β-catenin. At the membrane, independently of DSL ligands, Notch1 can antagonise β-catenin activity through an endocytic mechanism that requires its interaction with Deltex and sequesters β-catenin into the membrane fraction. Within the nucleus, the intracellular domain of Notch1 can also limit β-catenin induced transcription through the formation of a complex that requires its interaction with RBPjκ. We believe these mechanisms contribute to the robustness of cell-fate decisions by sharpening the distinction between opposing Notch/Wnt responses.
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http://dx.doi.org/10.1038/s41598-021-88618-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079408PMC
April 2021

Toll-like receptor 3 expression in myeloid cells is essential for efficient regeneration after acute pancreatitis in mice.

Eur J Immunol 2021 May 22;51(5):1182-1194. Epub 2021 Mar 22.

School of Medicine, Medizinische Klinik und Poliklinik II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Stringent regulation of the inflammatory response is crucial for normal tissue regeneration. Here, we analyzed the role of Toll-like receptor 3 (TLR3) in pancreatic regeneration after acute pancreatitis (AP). AP was induced by caerulein treatment in mice with global TLR3 deficiency (TLR3 ) or in mice re-expressing TLR3 exclusively in the myeloid cell lineage (TLR3 ). Compared to WT mice, TLR3 mice had a markedly increased formation of acinar-to-ductal metaplasia (ADM) that persisted until day 7 after initiation of AP. Pancreatic tissue of WT mice was completely regenerated after 5 days with no detectable ADM structures. The enhancing effect of TLR3-deficiency on ADM formation was closely linked with an increased and prolonged accumulation of macrophages in pancreata of TLR3 mice. Importantly, the phenotype of TLR3 mice was rescued in TLR3 mice, demonstrating the causative role of myeloid cell selective TLR3 signaling. Moreover, in vitro stimulation of macrophages through TLR3 initiated cell death by a caspase-8-associated mechanism. Therefore, these findings provide evidence that TLR3 signaling in myeloid cells is sufficient to limit inflammation and ADM formation and to promote regeneration after AP. Notably, resolution of inflammation after AP was associated with macrophage sensitivity to TLR3-mediated cell death.
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http://dx.doi.org/10.1002/eji.202048771DOI Listing
May 2021

Mir34a constrains pancreatic carcinogenesis.

Sci Rep 2020 06 15;10(1):9654. Epub 2020 Jun 15.

Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Munich, Germany.

Several studies have shown that over 70 different microRNAs are aberrantly expressed in pancreatic ductal adenocarcinoma (PDAC), affecting proliferation, apoptosis, metabolism, EMT and metastasis. The most important genetic alterations driving PDAC are a constitutive active mutation of the oncogene Kras and loss of function of the tumour suppressor Tp53 gene. Since the MicroRNA 34a (Mir34a) is a direct target of Tp53 it may critically contribute to the suppression of PDAC. Mir34a is epigenetically silenced in numerous cancers, including PDAC, where Mir34a down-regulation has been associated with poor patient prognosis. To determine whether Mir34a represents a suppressor of PDAC formation we generated an in vivo PDAC-mouse model harbouring pancreas-specific loss of Mir34a (Kras; Mir34a). Histological analysis of Kras; Mir34a mice revealed an accelerated formation of pre-neoplastic lesions and a faster PDAC development, compared to Kras controls. Here we show that the accelerated phenotype is driven by an early up-regulation of the pro-inflammatory cytokines TNFA and IL6 in normal acinar cells and accompanied by the recruitment of immune cells. Our results imply that Mir34a restrains PDAC development by modulating the immune microenvironment of PDAC, thus defining Mir34a restauration as a potential therapeutic strategy for inhibition of PDAC development.
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http://dx.doi.org/10.1038/s41598-020-66561-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295749PMC
June 2020

Loss of Wasl improves pancreatic cancer outcome.

JCI Insight 2020 05 21;5(10). Epub 2020 May 21.

Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Germany.

Several studies have suggested an oncogenic role for the neural Wiskott-Aldrich syndrome protein (N-WASP, encoded by the Wasl gene), but thus far, little is known about its function in pancreatic ductal adenocarcinoma (PDAC). In this study, we performed in silico analysis of WASL expression in PDAC patients and found a correlation between low WASL expression and prolonged survival. To clarify the role of Wasl in pancreatic carcinogenesis, we used 2 oncogenic Kras-based PDAC mouse models with pancreas-specific Wasl deletion. In line with human data, both mouse models had an increased survival benefit due to either impaired tumor development in the presence of the tumor suppressor Trp53 or the delayed tumor progression and senescent phenotype upon genetic ablation of Trp53. Mechanistically, loss of Wasl resulted in cell-autonomous senescence through displacement of the N-WASP binding partners WASP-interacting protein (WIP) and p120ctn; vesicular accumulation of GSK3β, as well as YAP1 and phosphorylated β-catenin, which are components of the destruction complex; and upregulation of Cdkn1a(p21), a master regulator of senescence. Our findings, thus, indicate that Wasl functions in an oncogenic manner in PDAC by promoting the deregulation of the p120-catenin/β-catenin/p21 pathway. Therefore, strategies to reduce N-WASP activity might improve the survival outcomes of PDAC patients.
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http://dx.doi.org/10.1172/jci.insight.127275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259520PMC
May 2020

Notch Signaling Mediates Differentiation in Barrett's Esophagus and Promotes Progression to Adenocarcinoma.

Gastroenterology 2020 08 20;159(2):575-590. Epub 2020 Apr 20.

Department of Medicine, Columbia University Irving Medical Center, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York.

Background & Aims: Studies are needed to determine the mechanism by which Barrett's esophagus (BE) progresses to esophageal adenocarcinoma (EAC). Notch signaling maintains stem cells in the gastrointestinal tract and is dysregulated during carcinogenesis. We explored the relationship between Notch signaling and goblet cell maturation, a feature of BE, during EAC pathogenesis.

Methods: We measured goblet cell density and levels of Notch messenger RNAs in BE tissues from 164 patients, with and without dysplasia or EAC, enrolled in a multicenter study. We analyzed the effects of conditional expression of an activated form of NOTCH2 (pL2.Lgr5.N2IC), conditional deletion of NOTCH2 (pL2.Lgr5.N2fl/fl), or loss of nuclear factor κB (NF-κB) (pL2.Lgr5.p65fl/fl), in Lgr5 (progenitor) cells in L2-IL1B mice (which overexpress interleukin 1 beta in esophagus and squamous forestomach and are used as a model of BE). We collected esophageal and stomach tissues and performed histology, immunohistochemistry, flow cytometry, transcriptome, and real-time polymerase chain reaction analyses. Cardia and forestomach tissues from mice were cultured as organoids and incubated with inhibitors of Notch or NF-kB.

Results: Progression of BE to EAC was associated with a significant reduction in goblet cell density comparing nondysplastic regions of tissues from patients; there was an inverse correlation between goblet cell density and levels of NOTCH3 and JAG2 messenger RNA. In mice, expression of the activated intracellular form of NOTCH2 in Lgr5 cells reduced goblet-like cell maturation, increased crypt fission, and accelerated the development of tumors in the squamocolumnar junction. Mice with deletion of NOTCH2 from Lgr5 cells had increased maturation of goblet-like cells, reduced crypt fission, and developed fewer tumors. Esophageal tissues from in pL2.Lgr5.N2IC mice had increased levels of RelA (which encodes the p65 unit of NF-κB) compared to tissues from L2-IL1B mice, and we found evidence of increased NF-κB activity in Lgr5 cells. Esophageal tissues from pL2.Lgr5.p65fl/fl mice had lower inflammation and metaplasia scores than pL2.Lgr5.N2IC mice. In organoids derived from pL2-IL1B mice, the NF-κB inhibitor JSH-23 reduced cell survival and proliferation.

Conclusions: Notch signaling contributes to activation of NF-κB and regulates differentiation of gastric cardia progenitor cells in a mouse model of BE. In human esophageal tissues, progression of BE to EAC was associated with reduced goblet cell density and increased levels of Notch expression. Strategies to block this pathway might be developed to prevent EAC in patients with BE.
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http://dx.doi.org/10.1053/j.gastro.2020.04.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484392PMC
August 2020

MEK Inhibition Targets Cancer Stem Cells and Impedes Migration of Pancreatic Cancer Cells and .

Stem Cells Int 2019 2;2019:8475389. Epub 2019 Jun 2.

Department of Internal Medicine I, Ulm University, Germany.

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease with a very poor prognosis. At the same time, its incidence is on the rise, and PDAC is expected to become the second leading cause of cancer-related death by 2030. Despite extensive work on new therapeutic approaches, the median overall survival is only 6-12 months after diagnosis and the 5-year survival is less than 7%. While pancreatic cancer is particularly difficult to treat, patients usually succumb not to the growth of the primary tumor, but to extensive metastasis; therefore, strategies to reduce the migratory and metastatic capacity of pancreatic cancer cells merit close attention. The vast majority of pancreatic cancers harbor RAS mutations. The outstanding relevance of the RAS/MEK/ERK pathway in pancreatic cancer biology has been extensively shown previously. Due to their high dependency on Ras mutations, pancreatic cancers might be particularly sensitive to inhibitors acting downstream of Ras. Herein, we use a genetically engineered mouse model of pancreatic cancer and primary pancreatic cancer cells were derived from this model to demonstrate that small-molecule MEK inhibitors functionally abrogate cancer stem cell populations as demonstrated by reduced sphere and organoid formation capacity. Furthermore, we demonstrate that MEK inhibition suppresses TGF-induced epithelial-to-mesenchymal transition and migration and ultimately results in a highly significant reduction in circulating tumor cells in mice.
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http://dx.doi.org/10.1155/2019/8475389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589314PMC
June 2019

The neuropeptide receptor subunit RAMP1 constrains the innate immune response during acute pancreatitis in mice.

Pancreatology 2019 Jun 11;19(4):541-547. Epub 2019 May 11.

Technical University of Munich, School of Medicine, Klinikum Rechts der Isar, Department of Internal Medicine II, Munich, Germany. Electronic address:

Objectives: The importance of the Calcitonin-gene-related-peptide-pathway (CGRP) as neuronal modulator of innate immune responses in mice has been previously demonstrated. The CGRP-receptor is composed of two subunits: the receptor-activity-modifying-protein-1 (RAMP1) and the calcitonin-receptor-like-receptor (CLR). CGRP can influence immune cells and their capacity of producing inflammatory cytokines. Using a RAMP1 knockout-mouse (RAMP1) we examined the role of the CGRP-receptor in the acute-phase of cerulein-induced pancreatitis.

Methods: Hourly cerulein-injections for a period of 8 h in RAMP1 and wild-type mice were performed. To compare severity and extent of inflammation in RAMP1 and wild-type mice, histological analyses were done and cytokine levels were assessed using qRT-PCR 8 h, 24 h, 2 days, and 7 days post-cerulein-treatment. Furthermore, serum activities of LDH and lipase were determined.

Results: After 8 h RAMP1 mice showed a higher pancreas-to-body-weight-ratio, increased tissue edema and immune cell infiltration with higher amount of F4/80-positive cells as compared to wild-type mice. Overall infiltration of immune cells at 24 h was increased in RAMP1 mice and composed predominantly of MPO-positive neutrophils. In addition, after 24 h RAMP1 mice presented a higher pancreas-to-body-weight-ratio, higher expression of Ccl3, Il6, and Il1b and increased number of cleaved caspase 3 positive cells. Serum lipase correlated with the extent of tissue damage in RAMP1 compared to wild-type mice 24 h post-cerulein treatment.

Conclusion: Mice lacking RAMP1 showed increased inflammation, tissue edema, and pancreas injury particularly in the early phase of acute pancreatitis. This study highlights the essential role of CGRP for dampening the innate immune response in acute pancreatitis.
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http://dx.doi.org/10.1016/j.pan.2019.05.455DOI Listing
June 2019

Atypical flat lesions derive from pancreatic acinar cells.

Pancreatology 2017 May - Jun;17(3):350-353. Epub 2017 Apr 25.

Institute of Pathology, University Clinic Duesseldorf, Heinrich-Heine University, Duesseldorf, Germany.

Objectives: Pancreatic ductal adenocarcinoma (PDAC) is thought to derive from different precursor lesions including the recently identified atypical flat lesions (AFL). While all precursor lesions and PDAC share ductal characteristics, there is an ongoing debate about the cellular origin of the different PDAC precursor lesions. In particular, pancreatic acinar cells have previously been shown to display a remarkable plasticity being able to undergo ductal dedifferentiation in the context of oncogenic stimuli.

Methods: Histological analyses were performed in a murine PDAC model that specifically expresses oncogenic Kras in adult pancreatic acinar cells. Occurrence, characterization, and lineage tracing of AFLs were investigated.

Results: Upon expression of oncogenic Kras in adult pancreatic acinar cells, AFLs with typical morphology and expression profile arise. Lineage tracing confirmed that the AFLs were of acinar origin.

Conclusions: Using a murine PDAC model, this study identifies pancreatic acinar cells as a cellular source for AFLs.
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http://dx.doi.org/10.1016/j.pan.2017.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770228PMC
March 2018

Oncogenic KRas-induced Increase in Fluid-phase Endocytosis is Dependent on N-WASP and is Required for the Formation of Pancreatic Preneoplastic Lesions.

EBioMedicine 2017 Feb 24;15:90-99. Epub 2016 Dec 24.

Clinic and Polyclinic for Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center, DKFZ, Heidelberg, Germany; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner Site Essen, West German Cancer Center, University Hospital Essen, Germany. Electronic address:

Fluid-phase endocytosis is a homeostatic process with an unknown role in tumor initiation. The driver mutation in pancreatic ductal adenocarcinoma (PDAC) is constitutively active KRas, which induces neoplastic transformation of acinar cells through acinar-to-ductal metaplasia (ADM). We have previously shown that KRas-induced ADM is dependent on RAC1 and EGF receptor (EGFR) by a not fully clarified mechanism. Using three-dimensional mouse and human acinar tissue cultures and genetically engineered mouse models, we provide evidence that (i) KRas leads to EGFR-dependent sustained fluid-phase endocytosis (FPE) during acinar metaplasia; (ii) variations in plasma membrane tension increase FPE and lead to ADM in vitro independently of EGFR; and (iii) that RAC1 regulates ADM formation partially through actin-dependent regulation of FPE. In addition, mice with a pancreas-specific deletion of the Neural-Wiskott-Aldrich syndrome protein (N-WASP), a regulator of F-actin, have reduced FPE and impaired ADM emphasizing the in vivo relevance of our findings. This work defines a new role of FPE as a tumor initiating mechanism.
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http://dx.doi.org/10.1016/j.ebiom.2016.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233824PMC
February 2017

Hes1 Controls Exocrine Cell Plasticity and Restricts Development of Pancreatic Ductal Adenocarcinoma in a Mouse Model.

Am J Pathol 2016 11 14;186(11):2934-2944. Epub 2016 Sep 14.

II Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany; German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany; Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. Electronic address:

Perturbation of pancreatic acinar cell state can lead to acinar-to-ductal metaplasia (ADM), a precursor lesion to the development of pancreatic ductal adenocarcinoma (PDAC). In the pancreas, Notch signaling is active both during development and in adult cellular differentiation processes. Hes1, a key downstream target of the Notch signaling pathway, is expressed in the centroacinar compartment of the adult pancreas as well as in both preneoplastic and malignant lesions. In this study, we used a murine genetic in vivo approach to ablate Hes1 in pancreatic progenitor cells (Ptf1a; Hes1). Using this model, we studied the role of Hes1 in both acinar cell plasticity and pancreatic regeneration after caerulein-induced pancreatitis and in Kras-driven PDAC development. We show that, although pancreatic development is not perturbed on the deletion of Hes1, terminal acinar differentiation in the adult pancreas is compromised. Moreover, the loss of Hes1 leads to the impaired regeneration of the exocrine compartment, accelerated fatty metaplasia, and persistent ADM after acute caerulein-induced pancreatitis. In Kras-driven carcinogenesis, Hes1 ablation resulted in increased ADM, decreased formation of high-grade pancreatic intraepithelial neoplasias, and accelerated development of PDAC with shortened survival time. In conclusion, Hes1 plays a key role in acinar cell integrity and plasticity on cellular insults. Furthermore, Hes1 is an essential component of the pancreatic intraepithelial neoplasias-to-PDAC route in Kras-driven mouse pancreatic carcinogenesis.
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http://dx.doi.org/10.1016/j.ajpath.2016.07.025DOI Listing
November 2016

Membranous CD24 drives the epithelial phenotype of pancreatic cancer.

Oncotarget 2016 Aug;7(31):49156-49168

II. Medizinische Klinik und Poliklinik, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany.

Surface CD24 has previously been described, together with CD44 and ESA, for the characterization of putative cancer stem cells in pancreatic ductal adenocarcinoma (PDAC), the most fatal of all solid tumors. CD24 has a variety of biological functions including the regulation of invasiveness and cell proliferation, depending on the tumor entity and subcellular localization. Genetically engineered mouse models (GEMM) expressing oncogenic KrasG12D recapitulate the human disease and develop PDAC. In this study we investigate the function of CD24 using GEMM of endogenous PDAC and a model of cerulein-induced acute pancreatitis. We found that (i) CD24 expression was upregulated in murine and human PDAC and during acute pancreatitis (ii) CD24 was expressed exclusively in differentiated PDAC, whereas CD24 absence was associated with undifferentiated tumors and (iii) membranous CD24 expression determines tumor subpopulations with an epithelial phenotype in grafted models. In addition, we show that CD24 protein is stabilized in response to WNT activation and that overexpression of CD24 in pancreatic cancer cells upregulated β-catenin expression augmenting an epithelial, non-metastatic signature. Our results support a positive feedback model according to which (i) WNT activation and subsequent β-catenin dephosphorylation stabilize CD24 protein expression, and (ii) sustained CD24 expression upregulates β-catenin expression. Eventually, membranous CD24 augments the epithelial phenotype of pancreatic tumors. Thus we link the WNT/β-catenin pathway with the regulation of CD24 in the context of PDAC differentiation.
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http://dx.doi.org/10.18632/oncotarget.9402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226498PMC
August 2016

Wnt-Notch signalling crosstalk in development and disease.

Cell Mol Life Sci 2014 Sep 19;71(18):3553-67. Epub 2014 Jun 19.

Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK,

The Notch and Wnt pathways are two of only a handful of highly conserved signalling pathways that control cell-fate decisions during animal development (Pires-daSilva and Sommer in Nat Rev Genet 4: 39-49, 2003). These two pathways are required together to regulate many aspects of metazoan development, ranging from germ layer patterning in sea urchins (Peter and Davidson in Nature 474: 635-639, 2011) to the formation and patterning of the fly wing (Axelrod et al in Science 271:1826-1832, 1996; Micchelli et al in Development 124:1485-1495, 1997; Rulifson et al in Nature 384:72-74, 1996), the spacing of the ciliated cells in the epidermis of frog embryos (Collu et al in Development 139:4405-4415, 2012) and the maintenance and turnover of the skin, gut lining and mammary gland in mammals (Clayton et al in Nature 446:185-189, 2007; Clevers in Cell 154:274-284, 2013; Doupe et al in Dev Cell 18:317-323, 2010; Lim et al in Science 342:1226-1230, 2013; Lowell et al in Curr Biol 10:491-500, 2000; van et al in Nature 435:959-963, 2005; Yin et al in Nat Methods 11:106-112, 2013). In addition, many diseases, including several cancers, are caused by aberrant signalling through the two pathways (Bolós et al in Endocr Rev 28: 339-363, 2007; Clevers in Cell 127: 469-480, 2006). In this review, we will outline the two signalling pathways, describe the different points of interaction between them, and cover how these interactions influence development and disease.
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http://dx.doi.org/10.1007/s00018-014-1644-xDOI Listing
September 2014

Dishevelled limits Notch signalling through inhibition of CSL.

Development 2012 Dec;139(23):4405-15

Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.

Notch and Wnt are highly conserved signalling pathways that are used repeatedly throughout animal development to generate a diverse array of cell types. However, they often have opposing effects on cell-fate decisions with each pathway promoting an alternate outcome. Commonly, a cell receiving both signals exhibits only Wnt pathway activity. This suggests that Wnt inhibits Notch activity to promote a Wnt-ON/Notch-OFF output; but what might underpin this Notch regulation is not understood. Here, we show that Wnt acts via Dishevelled to inhibit Notch signalling, and that this crosstalk regulates cell-fate specification in vivo during Xenopus development. Mechanistically, Dishevelled binds and directly inhibits CSL transcription factors downstream of Notch receptors, reducing their activity. Furthermore, our data suggest that this crosstalk mechanism is conserved between vertebrate and invertebrate homologues. Thus, we identify a dual function for Dishevelled as an inhibitor of Notch signalling and an activator of the Wnt pathway that sharpens the distinction between opposing Wnt and Notch responses, allowing for robust cell-fate decisions.
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http://dx.doi.org/10.1242/dev.081885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509734PMC
December 2012

Rapid cleavage of RNA by RNase E in the absence of 5' monophosphate stimulation.

Mol Microbiol 2010 May 2;76(3):590-604. Epub 2009 Nov 2.

Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, LS2 9JT, England, UK.

The best characterized pathway for the initiation of mRNA degradation in Escherichia coli involves the removal of the 5'-terminal pyrophosphate to generate a monophosphate group that stimulates endonucleolytic cleavage by RNase E. We show here however, using well-characterized oligonucleotide substrates and mRNA transcripts, that RNase E can cleave certain RNAs rapidly without requiring a 5'-monophosphorylated end. Moreover, the minimum substrate requirement for this mode of cleavage, which can be categorized as 'direct' or 'internal' entry, appears to be multiple single-stranded segments in a conformational context that allows their simultaneous interaction with RNase E. While previous work has alluded to the existence of a 5' end-independent mechanism of mRNA degradation, the relative simplicity of the requirements identified here for direct entry suggests that it could represent a major means by which mRNA degradation is initiated in E. coli and other organisms that contain homologues of RNase E. Our results have implications for the interplay of translation and mRNA degradation and models of gene regulation by small non-coding RNAs.
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http://dx.doi.org/10.1111/j.1365-2958.2009.06935.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948425PMC
May 2010
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