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https://www.readbyqxmd.com/read/28709000/regulatory-expansion-in-mammals-of-multivalent-hnrnp-assemblies-that-globally-control-alternative-splicing
#1
Serge Gueroussov, Robert J Weatheritt, Dave O'Hanlon, Zhen-Yuan Lin, Ashrut Narula, Anne-Claude Gingras, Benjamin J Blencowe
Alternative splicing (AS) patterns have diverged rapidly during vertebrate evolution, yet the functions of most species- and lineage-specific splicing events are not known. We observe that mammalian-specific AS events are enriched in transcript sequences encoding intrinsically disordered regions (IDRs) of proteins, in particular those containing glycine/tyrosine repeats that mediate formation of higher-order protein assemblies implicated in gene regulation and human disease. These evolutionary changes impact nearly all members of the hnRNP A and D families of RNA binding proteins...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28666471/heterogeneous-ribonuclear-protein-e2-hnrnp-e2-is-associated-with-tdp-43-immunoreactive-neurites-in-semantic-dementia-but-not-with-other-tdp-43-pathological-subtypes-of-frontotemporal-lobar-degeneration
#2
Yvonne S Davidson, Andrew C Robinson, Louis Flood, Sara Rollinson, Bridget C Benson, Yasmine T Asi, Anna Richardson, Matthew Jones, Julie S Snowden, Stuart Pickering-Brown, Tammaryn Lashley, David M A Mann
Frontotemporal Lobar Degeneration (FTLD) encompasses certain related neurodegenerative disorders which alter personality and cognition. Heterogeneous ribonuclear proteins (hnRNPs) maintain RNA metabolism and changes in their function may underpin the pathogenesis of FTLD. Immunostaining for hnRNP E2 was performed on sections of frontal and temporal cortex with hippocampus from 80 patients with FTLD, stratified by pathology into FTLD-tau and FTLD-TDP type A, B and C subtypes, and by genetics into patients with C9orf72 expansions, MAPT or GRN mutations, or those with no known mutation, and on 10 healthy controls...
June 30, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28650318/tandem-hnrnp-a1-rna-recognition-motifs-act-in-concert-to-repress-the-splicing-of-survival-motor-neuron-exon-7
#3
Irene Beusch, Pierre Barraud, Ahmed Moursy, Antoine Cléry, Frédéric Hai-Trieu Allain
HnRNP A1 regulates many alternative splicing events by the recognition of splicing silencer elements. Here, we provide the solution structures of its two RNA recognition motifs (RRMs) in complex with short RNA. In addition, we show by NMR that both RRMs of hnRNP A1 can bind simultaneously to a single bipartite motif of the human intronic splicing silencer ISS-N1, which controls survival of motor neuron exon 7 splicing. RRM2 binds to the upstream motif and RRM1 to the downstream motif. Combining the insights from the structure with in cell splicing assays we show that the architecture and organization of the two RRMs is essential to hnRNP A1 function...
June 26, 2017: ELife
https://www.readbyqxmd.com/read/28629158/contribution-of-the-degeneration-of-the-neuro-axonal-unit-to-the-pathogenesis-of-multiple-sclerosis
#4
REVIEW
Hannah E Salapa, Sangmin Lee, Yoojin Shin, Michael C Levin
Multiple sclerosis (MS) is a demyelinating, autoimmune disease of the central nervous system. In recent years, it has become more evident that neurodegeneration, including neuronal damage and axonal injury, underlies permanent disability in MS. This manuscript reviews some of the mechanisms that could be responsible for neurodegeneration and axonal damage in MS and highlights the potential role that dysfunctional heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and antibodies to hnRNP A1 may play in MS pathogenesis...
June 18, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28625847/hnrnp-a1-alters-the-structure-of-a-conserved-enterovirus-ires-domain-to-stimulate-viral-translation
#5
Michele Tolbert, Christopher E Morgan, Marvin Pollum, Carlos E Crespo-Hernández, Mei-Ling Li, Gary Brewer, Blanton S Tolbert
Enteroviruses use a type I IRES structure to facilitate protein synthesis and promote genome replication. Type I IRES elements require auxiliary host proteins to organize RNA structure for 40S ribosomal subunit assembly. Heterogeneous nuclear ribonucleoprotein A1 stimulates Enterovirus 71 (EV71) translation in part through specific interactions with its stem loop II (SLII) IRES domain. Here, we determined a conjoined NMR-SAXS structure of the EV71 SLII domain and a mutant that significantly attenuates viral replication by abrogating hnRNP A1 interactions...
June 15, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28600288/tcr-signal-strength-regulates-akt-substrate-specificity-to-induce-alternate-murine-th-and-t-regulatory-cell-differentiation-programs
#6
William F Hawse, William C Boggess, Penelope A Morel
The Akt/mTOR pathway is a key driver of murine CD4(+) T cell differentiation, and induction of regulatory T (Treg) cells results from low TCR signal strength and low Akt/mTOR signaling. However, strong TCR signals induce high Akt activity that promotes Th cell induction. Yet, it is unclear how Akt controls alternate T cell fate decisions. We find that the strength of the TCR signal results in differential Akt enzymatic activity. Surprisingly, the Akt substrate networks associated with T cell fate decisions are qualitatively different...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28592492/heterogeneous-nuclear-ribonucleoprotein-k-inhibits-heat-shock-induced-transcriptional-activity-of-heat-shock-factor-1
#7
Hee-Jung Kim, Jae-Jin Lee, Jin-Hwan Cho, Jaeho Jeong, A Young Park, Wonmo Kang, Kong-Joo Lee
When cells are exposed to heat shock and various other stresses, heat shock factor 1 (HSF1) is activated and the heat shock response (HSR) is elicited. To better understand the molecular regulation of the HSR, we used 2D-PAGE based proteome analysis to screen for heat shock-induced posttranslationally modified cellular proteins. Our analysis revealed that two protein spots typically present on 2D-PAGE gels and containing heterogeneous nuclear ribonucleoprotein K (hnRNP K) with trioxidized Cys132 disappeared after the heat shock treatment and reappeared during recovery, but the total amount of hnRNP K protein remained unchanged...
June 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28588612/the-roles-of-carcinoembryonic-antigen-in-liver-metastasis-and-therapeutic-approaches
#8
REVIEW
Joo Han Lee, Seong-Wook Lee
Metastasis is a highly complicated and sequential process in which primary cancer spreads to secondary organic sites. Liver is a well-known metastatic organ from colorectal cancer. Carcinoembryonic antigen (CEA) is expressed in most gastrointestinal, breast, and lung cancer cells. Overexpression of CEA is closely associated with liver metastasis, which is the main cause of death from colorectal cancer. CEA is widely used as a diagnostic and prognostic tumor marker in cancer patients. It affects many steps of liver metastasis from colorectal cancer cells...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28575377/major-hnrnp-proteins-act-as-general-tdp-43-functional-modifiers-both-in-drosophila-and-human-neuronal-cells
#9
Chiara Appocher, Fatemeh Mohagheghi, Sara Cappelli, Cristiana Stuani, Maurizio Romano, Fabian Feiguin, Emanuele Buratti
Nuclear factor TDP-43 is known to play an important role in several neurodegenerative pathologies. In general, TDP-43 is an abundant protein within the eukaryotic nucleus that binds to many coding and non-coding RNAs and influence their processing. Using Drosophila, we have performed a functional screening to establish the ability of major hnRNP proteins to affect TDP-43 overexpression/depletion phenotypes. Interestingly, we observed that lowering hnRNP and TDP-43 expression has a generally harmful effect on flies locomotor abilities...
May 31, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28570076/insight-into-the-complexity-of-the-i-motif-and-g-quadruplex-dna-structures-formed-in-the-kras-promoter-and-subsequent-drug-induced-gene-repression
#10
Christine E Kaiser, Natalie A Van Ert, Prashansa Agrawal, Reena Chawla, Danzhou Yang, Laurence H Hurley
Activating KRAS mutations frequently occur in pancreatic, colorectal, and lung adenocarcinomas. While many attempts have been made to target oncogenic KRAS, no clinically useful therapies currently exist. Most efforts to target KRAS have focused on inhibiting the mutant protein; a less explored approach involves targeting KRAS at the transcriptional level. The promoter element of the KRAS gene contains a GC-rich nuclease hypersensitive site with three potential DNA secondary structure-forming regions. These are referred to as the Near-, Mid-, and Far-regions, on the basis of their proximity to the transcription start site...
June 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28560430/fyn-heterogeneous-nuclear-ribonucleoprotein-e1-signaling-regulates-pancreatic-cancer-metastasis-by-affecting-the-alternative-splicing-of-integrin-%C3%AE-1
#11
Peng Jiang, Zhonghu Li, Feng Tian, Xiaowu Li, Jin Yang
Pancreatic cancer is characterized by a dense desmoplastic reaction in which extracellular matrix proteins accumulate and surround tumor cells. Integrins and their related signaling molecules are associated with progression of pancreatic cancer. In the present study, the association between the metastasis of pancreatic cancer and the expression of hnRNP E1 and integrin β1 was evaluated. In vitro and in vivo experiments were designed to study the mechanism underlying the regulation of integrin β1 splicing by the Fyn/hnRNP E1 spliceosome...
July 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28559488/viral-dna-replication-orientation-and-hnrnps-regulate-transcription-of-the-human-papillomavirus-18-late-promoter
#12
Xiaohong Wang, Haibin Liu, Hui Ge, Masahiko Ajiro, Nishi R Sharma, Craig Meyers, Pavel Morozov, Thomas Tuschl, Amar Klar, Donald Court, Zhi-Ming Zheng
The life cycle of human papillomaviruses (HPVs) is tightly linked to keratinocyte differentiation. Although expression of viral early genes is initiated immediately upon virus infection of undifferentiated basal cells, viral DNA amplification and late gene expression occur only in the mid to upper strata of the keratinocytes undergoing terminal differentiation. In this report, we show that the relative activity of HPV18 TATA-less late promoter P811 depends on its orientation relative to that of the origin (Ori) of viral DNA replication and is sensitive to the eukaryotic DNA polymerase inhibitor aphidicolin...
May 30, 2017: MBio
https://www.readbyqxmd.com/read/28549443/quantitative-analysis-of-cryptic-splicing-associated-with-tdp-43-depletion
#13
Jack Humphrey, Warren Emmett, Pietro Fratta, Adrian M Isaacs, Vincent Plagnol
BACKGROUND: Reliable exon recognition is key to the splicing of pre-mRNAs into mature mRNAs. TDP-43 is an RNA-binding protein whose nuclear loss and cytoplasmic aggregation are a hallmark pathology in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). TDP-43 depletion causes the aberrant inclusion of cryptic exons into a range of transcripts, but their extent, relevance to disease pathogenesis and whether they are caused by other RNA-binding proteins implicated in ALS/FTD are unknown...
May 26, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28523741/comparative-membrane-proteomics-analyses-of-breast-cancer-cell-lines-to-understand-the-molecular-mechanism-of-breast-cancer-brain-metastasis
#14
Wenjing Peng, Yu Zhang, Rui Zhu, Yehia Mechref
Breast cancer is the leading type of cancer in women. Breast cancer brain metastasis is currently considered an issue of concern among breast cancer patients. Membrane proteins play important roles in breast cancer brain metastasis, involving cell adhesion and penetration of blood-brain barrier. To understand the mechanism of breast cancer brain metastasis, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in conjunction with enrichment of membrane proteins to analyze the proteomes from 5 different breast cancer and a brain cancer cell lines...
May 19, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28520992/interplay-between-mir-574-3p-and-hnrnp-l-regulates-vegfa-mrna-translation-and-tumorigenesis
#15
Peng Yao, Jiangbin Wu, Daniel Lindner, Paul L Fox
MicroRNAs (miRNAs) and heterogeneous nuclear ribonucleoproteins (hnRNPs) are families of sequence-specific, posttranscriptional modulators of gene expression. Despite extensive mechanistic and functional studies on both regulatory classes, the interactions and crosstalk between them are largely unexplored. We have reported that competition between miR-297 and hnRNP L to bind a 3΄UTR-localized CA-rich element (CARE) of VEGFA mRNA regulates its translation. Here, we show that translation of VEGFA mRNA in human myeloid cells is dictated by a bi-directional interaction between miR-574-3p, a CA-rich microRNA, and hnRNP L...
May 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28510424/structure-dependent-binding-of-hnrnpa1-to-telomere-rna
#16
Xiao Liu, Takumi Ishizuka, Hong-Liang Bao, Kei Wada, Yuma Takeda, Keisuke Iida, Kazuo Nagasawa, Danzhou Yang, Yan Xu
Telomeric repeat-containing RNA is a new noncoding RNA molecule that performs various biofunctions. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is an RNA-binding protein involved in the telomere maintenance machinery. To date, little is known about how hnRNPA1 binds to telomeric RNA. In this study, we investigated the binding affinity and recognition mechanism of telomere RNA with the RNA recognition motif of hnRNPA1. Using the photochemical cross-linking method, we showed that the telomere RNA G-quadruplex with loops is important in the interaction of telomere RNA with hnRNPA1...
June 7, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28460002/proteomic-analysis-of-polyribosomes-identifies-splicing-factors-as-potential-regulators-of-translation-during-mitosis
#17
Ranen Aviner, Sarah Hofmann, Tamar Elman, Anjana Shenoy, Tamar Geiger, Ran Elkon, Marcelo Ehrlich, Orna Elroy-Stein
Precise regulation of mRNA translation is critical for proper cell division, but little is known about the factors that mediate it. To identify mRNA-binding proteins that regulate translation during mitosis, we analyzed the composition of polysomes from interphase and mitotic cells using unbiased quantitative mass-spectrometry (LC-MS/MS). We found that mitotic polysomes are enriched with a subset of proteins involved in RNA processing, including alternative splicing and RNA export. To demonstrate that these may indeed be regulators of translation, we focused on heterogeneous nuclear ribonucleoprotein C (hnRNP C) as a test case and confirmed that it is recruited to elongating ribosomes during mitosis...
June 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28456680/splicing-regulatory-factors-ageing-and-age-related-disease
#18
REVIEW
Eva Latorre, Lorna W Harries
Alternative splicing is a co-transcriptional process, which allows for the production of multiple transcripts from a single gene and is emerging as an important control point for gene expression. Alternatively expressed isoforms often have antagonistic function and differential temporal or spatial expression patterns, yielding enormous plasticity and adaptability to cells and increasing their ability to respond to environmental challenge. The regulation of alternative splicing is critical for numerous cellular functions in both pathological and physiological conditions, and deregulated alternative splicing is a key feature of common chronic diseases...
April 26, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28454091/heterogeneous-nuclear-ribonucleoprotein-hnrnp-l-promotes-dna-damage-induced-cell-apoptosis-by-enhancing-the-translation-of-p53
#19
Ji-Young Seo, Do-Yeon Kim, Seong-Hoon Kim, Hyo-Jin Kim, Hye Guk Ryu, Juhyun Lee, Kyung-Ha Lee, Kyong-Tai Kim
The tumor suppressor p53 is an essential gene in the induction of cell cycle arrest, DNA repair, and apoptosis. p53 protein is induced under cellular stress, blocking cell cycle progression and inducing DNA repair. Under DNA damage conditions, it has been reported that post-transcriptional regulation of p53 mRNA contributes to the increase in p53 protein level. Here we demonstrate that heterogeneous nuclear ribonucleoprotein (hnRNP) L enhances p53 mRNA translation. We found that hnRNP L is increased and binds to the 5'UTR of p53 mRNA in response to DNA damage...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28450158/the-erbb-family-and-androgen-receptor-signaling-are-targets-of%C3%A2-celecoxib-in-prostate-cancer
#20
Antonella Brizzolara, Roberto Benelli, Roberta Venè, Paola Barboro, Alessandro Poggi, Francesca Tosetti, Nicoletta Ferrari
Inflammation plays a central role in prostate cancer (PCa) development through significant crosstalk between the COX-2-ErbB family receptor network and androgen receptor (AR)-EGFR signaling pathways. The purpose of this work was to determine the ability of the COX-2 inhibitor Celecoxib to modulate the EGFR-AR signaling pathway in androgen-dependent PCa cells and to provide a rationale for its beneficial use in chemopreventive strategies. Functional studies of Celecoxib activity were performed on LNCaP prostate cancer cells...
April 25, 2017: Cancer Letters
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