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JOURNAL ARTICLE
Alexander Bampton, Ariana Gatt, Jack Humphrey, Sara Cappelli, Dipanjan Bhattacharya, Sandrine Foti, Anna-Leigh Brown, Yasmine Asi, Yi Hua Low, Marco Foiani, Towfique Raj, Emanuele Buratti, Pietro Fratta, Tammaryn Lashley
Heterogeneous nuclear ribonucleoproteins (HnRNPs) are a group of ubiquitously expressed RNA-binding proteins implicated in the regulation of all aspects of nucleic acid metabolism. HnRNP K is a member of this highly versatile hnRNP family. Pathological redistribution of hnRNP K to the cytoplasm has been linked to the pathogenesis of several malignancies but, until now, has been underexplored in the context of neurodegenerative disease. Here we show hnRNP K mislocalisation in pyramidal neurons of the frontal cortex to be a novel neuropathological feature that is associated with both frontotemporal lobar degeneration and ageing...
October 2021: Acta Neuropathologica
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JOURNAL ARTICLE
Bidyut K Mohanty, Joseph Aq Karam, Breege V Howley, Annamarie C Dalton, Simon Grelet, Toros Dincman, William S Streitfeld, Je-Hyun Yoon, Lata Balakrishnan, Walter J Chazin, David T Long, Philip H Howe
Heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) is a tumor suppressor protein that binds site- and structure-specifically to RNA sequences to regulate mRNA stability, facilitate alternative splicing, and suppress protein translation on several metastasis-associated mRNAs. Here, we show that hnRNP E1 binds polycytosine-rich DNA tracts present throughout the genome, including those at promoters of several oncogenes and telomeres and monitors genome integrity. It binds DNA in a site- and structure-specific manner...
September 2021: Life Science Alliance
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JOURNAL ARTICLE
Jyoti Batra, Hiroyuki Mori, Gabriel I Small, Manu Anantpadma, Olena Shtanko, Nawneet Mishra, Mengru Zhang, Dandan Liu, Caroline G Williams, Nadine Biedenkopf, Stephan Becker, Michael L Gross, Daisy W Leung, Robert A Davey, Gaya K Amarasinghe, Nevan J Krogan, Christopher F Basler
The Ebola virus VP30 protein interacts with the viral nucleoprotein and with host protein RBBP6 via PPxPxY motifs that adopt non-canonical orientations, as compared to other proline-rich motifs. An affinity tag-purification mass spectrometry approach identified additional PPxPxY-containing host proteins hnRNP L, hnRNPUL1, and PEG10, as VP30 interactors. hnRNP L and PEG10, like RBBP6, inhibit viral RNA synthesis and EBOV infection, whereas hnRNPUL1 enhances. RBBP6 and hnRNP L modulate VP30 phosphorylation, increase viral transcription, and exert additive effects on viral RNA synthesis...
July 14, 2021: EMBO Journal
#44
REVIEW
Xinyun Chen, Jianwen Yin, Dayan Cao, Deyong Xiao, Zhongjun Zhou, Ying Liu, Weinian Shou
RNA binding proteins (RBPs) have a broad biological and physiological function and are critical in regulating pre-mRNA posttranscriptional processing, intracellular migration, and mRNA stability. QKI, also known as Quaking, is a member of the signal transduction and activation of RNA (STAR) family, which also belongs to the heterogeneous nuclear ribonucleoprotein K- (hnRNP K-) homology domain protein family. There are three major alternatively spliced isoforms, QKI-5, QKI-6, and QKI-7, differing in carboxy-terminal domains...
2021: Frontiers in Cell and Developmental Biology
#45
JOURNAL ARTICLE
Peng Wang, Xinze Liu, Qi Li, Jue Wang, Wenke Ruan
Japanese encephalitis is a zoonotic disease caused by Japanese encephalitis virus (JEV). JEV nonstructural protein 1 (NS1) is involved in many crucial biological events during viral infection and immune suppression. To investigate the role of JEV NS1 in virus-infected cells, the molecules with which it interacts intracellularly were screened with a pull-down assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The interaction between heterogeneous nuclear ribonucleoprotein K (hnRNP K), vimentin and NS1 were verified with coimmunoprecipitation and confocal assays...
June 24, 2021: Virus Research
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JOURNAL ARTICLE
Karina Stringhetta Padovani, Renata Nishida Goto, Lais Brigliadori Fugio, Cristiana Bernadelli Garcia, Vani Maria Alves, Maria Sol Brassesco, Lewis Joel Greene, Eduardo Magalhães Rego, Andréia Machado Leopoldino
HnRNP K protein is a heterogeneous nuclear ribonucleoprotein which has been proposed to be involved in the leukemogenesis of acute promyelocytic leukemia (APL), as well as in differentiation induced by all-trans retinoic acid (ATRA). We previously demonstrated a connection between SET and hnRNP K function in head and neck squamous cell carcinoma (HNSCC) cells related to splicing processing. The objective of this study was to characterize the participation of hnRNP K and SET proteins in ATRA-induced differentiation in APL...
May 31, 2021: FEBS Open Bio
#47
REVIEW
Alejandro Velázquez-Cruz, Blanca Baños-Jaime, Antonio Díaz-Quintana, Miguel A De la Rosa, Irene Díaz-Moreno
Cell signaling mechanisms modulate gene expression in response to internal and external stimuli. Cellular adaptation requires a precise and coordinated regulation of the transcription and translation processes. The post-transcriptional control of mRNA metabolism is mediated by the so-called RNA-binding proteins (RBPs), which assemble with specific transcripts forming messenger ribonucleoprotein particles of highly dynamic composition. RBPs constitute a class of trans -acting regulatory proteins with affinity for certain consensus elements present in mRNA molecules...
2021: Frontiers in Molecular Biosciences
#48
JOURNAL ARTICLE
Shahid Banday, Raj K Pandita, Arjamand Mushtaq, Albino Bacolla, Ulfat Syed Mir, Dharmendra Kumar Singh, Sadaf Jan, Krishna P Bhat, Clayton R Hunt, Ganesh Rao, Vijay K Charaka, John A Tainer, Tej K Pandita, Mohammad Altaf
Vigilin (Vgl1) is essential for heterochromatin formation, chromosome segregation, and mRNA stability and is associated with autism spectrum disorders and cancer: vigilin, for example, can suppress proto-oncogene c- fms expression in breast cancer. Conserved from yeast to humans, vigilin is an RNA-binding protein with 14 tandemly arranged nonidentical hnRNP K-type homology (KH) domains. Here, we report that vigilin depletion increased cell sensitivity to cisplatin- or ionizing radiation (IR)-induced cell death and genomic instability due to defective DNA repair...
June 23, 2021: Molecular and Cellular Biology
#49
REVIEW
Prerna Malaney, María Velasco-Estevez, Pedro Aguilar-Garrido, Marisa J L Aitken, Lauren E Chan, Xiaorui Zhang, Sean M Post, Miguel Gallardo
B-cell lymphomas are one of the most biologically and molecularly heterogeneous group of malignancies. The inherent complexity of this cancer subtype necessitates the development of appropriate animal model systems to characterize the disease with the ultimate objective of identifying effective therapies. In this article, we discuss a new driver of B-cell lymphomas - hnRNP K (heterogenous nuclear ribonucleoprotein K)-an RNA-binding protein. We introduce the Eµ-Hnrnpk mouse model, a murine model characterized by hnRNP K overexpression in B cells, which develops B-cell lymphomas with high penetrance...
2021: Frontiers in Immunology
#50
JOURNAL ARTICLE
Madelyn A Gillentine, Tianyun Wang, Kendra Hoekzema, Jill Rosenfeld, Pengfei Liu, Hui Guo, Chang N Kim, Bert B A De Vries, Lisenka E L M Vissers, Magnus Nordenskjold, Malin Kvarnung, Anna Lindstrand, Ann Nordgren, Jozef Gecz, Maria Iascone, Anna Cereda, Agnese Scatigno, Silvia Maitz, Ginevra Zanni, Enrico Bertini, Christiane Zweier, Sarah Schuhmann, Antje Wiesener, Micah Pepper, Heena Panjwani, Erin Torti, Farida Abid, Irina Anselm, Siddharth Srivastava, Paldeep Atwal, Carlos A Bacino, Gifty Bhat, Katherine Cobian, Lynne M Bird, Jennifer Friedman, Meredith S Wright, Bert Callewaert, Florence Petit, Sophie Mathieu, Alexandra Afenjar, Celenie K Christensen, Kerry M White, Orly Elpeleg, Itai Berger, Edward J Espineli, Christina Fagerberg, Charlotte Brasch-Andersen, Lars Kjærsgaard Hansen, Timothy Feyma, Susan Hughes, Isabelle Thiffault, Bonnie Sullivan, Shuang Yan, Kory Keller, Boris Keren, Cyril Mignot, Frank Kooy, Marije Meuwissen, Alice Basinger, Mary Kukolich, Meredith Philips, Lucia Ortega, Margaret Drummond-Borg, Mathilde Lauridsen, Kristina Sorensen, Anna Lehman, Elena Lopez-Rangel, Paul Levy, Davor Lessel, Timothy Lotze, Suneeta Madan-Khetarpal, Jessica Sebastian, Jodie Vento, Divya Vats, L Manace Benman, Shane Mckee, Ghayda M Mirzaa, Candace Muss, John Pappas, Hilde Peeters, Corrado Romano, Maurizio Elia, Ornella Galesi, Marleen E H Simon, Koen L I van Gassen, Kara Simpson, Robert Stratton, Sabeen Syed, Julien Thevenon, Irene Valenzuela Palafoll, Antonio Vitobello, Marie Bournez, Laurence Faivre, Kun Xia, Rachel K Earl, Tomasz Nowakowski, Raphael A Bernier, Evan E Eichler
BACKGROUND: With the increasing number of genomic sequencing studies, hundreds of genes have been implicated in neurodevelopmental disorders (NDDs). The rate of gene discovery far outpaces our understanding of genotype-phenotype correlations, with clinical characterization remaining a bottleneck for understanding NDDs. Most disease-associated Mendelian genes are members of gene families, and we hypothesize that those with related molecular function share clinical presentations. METHODS: We tested our hypothesis by considering gene families that have multiple members with an enrichment of de novo variants among NDDs, as determined by previous meta-analyses...
April 19, 2021: Genome Medicine
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JOURNAL ARTICLE
The Long Linker Region of Telomere-Binding Protein TRF2 Is Responsible for Interactions with Lamins.
Aleksandra O Travina, Nadya V Ilicheva, Alexey G Mittenberg, Sergey V Shabelnikov, Anastasia V Kotova, Olga I Podgornaya
Telomere-binding factor 2 (TRF2) is part of the shelterin protein complex found at chromosome ends. Lamin A/C interacts with TRF2 and influences telomere position. TRF2 has an intrinsically disordered region between the ordered dimerization and DNA-binding domains. This domain is referred to as the long linker region of TRF2, or udTRF2. We suggest that udTRF2 might be involved in the interaction between TRF2 and lamins. The recombinant protein corresponding to the udTRF2 region along with polyclonal antibodies against this region were used in co-immunoprecipitation with purified lamina and nuclear extracts...
March 24, 2021: International Journal of Molecular Sciences
#52
JOURNAL ARTICLE
Paul Kwangho Kwon, Hyo-Min Kim, Byunghee Kang, Sung Wook Kim, Sung-Min Hwang, Sin-Hyeog Im, Tae-Young Roh, Kyong-Tai Kim
Retinoic acid-related orphan receptor γ (RORγ) maintains the circadian rhythms of its downstream genes. However, the mechanism behind the transcriptional activation of RORγ itself remains unclear. Here, we demonstrate that transcription of RORγ is activated by heterogeneous nuclear ribonucleoprotein K (hnRNP K) via the poly(C) motif within its proximal promoter. Interestingly, we confirmed the binding of endogenous hnRNP K within RORγ1 and RORγ2 promoter along with the recruitment of RNA polymerase 2 through chromatin immunoprecipitation (ChIP)...
April 2021: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
#53
JOURNAL ARTICLE
Matthew S Alexander, Rylie M Hightower, Andrea L Reid, Alexis H Bennett, Lakshmanan Iyer, Donna K Slonim, Madhurima Saha, Genri Kawahara, Louis M Kunkel, Alan S Kopin, Vandana A Gupta, Peter B Kang, Isabelle Draper
INTRODUCTION/AIMS: RNA binding proteins (RBPs) play an important role in skeletal muscle development and disease by regulating RNA splicing. In myotonic dystrophy type 1 (DM1), the RBP MBNL1 (Muscleblind-like) is sequestered by toxic CUG repeats, leading to mis-splicing of MBNL1 targets. Mounting evidence from the literature has implicated other factors in the pathogenesis of DM1. Here we sought to evaluate the functional role of hnRNP L in normal and DM1 muscle cells. We sought to test if modulation of hnRNP L expression affected DM1 splicing targets and myogenic outcomes...
March 2, 2021: Muscle & Nerve
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JOURNAL ARTICLE
Gaochun Zhu, Qian Zhu, Wei Zhang, Chen Hui, Yuwen Li, Meiyuan Yang, Shimin Pang, Yaobing Li, Guoyong Xue, Hongping Chen
Synaptic plasticity plays an important role in learning and memory in the developing hippocampus. However, the precise molecular mechanism in lead exposure models remains to be studied. UCP2, an inner mitochondrial anion carrier, regulates synaptic plasticity through uncoupling neurons. And hnRNP K, an RNA binding protein, plays a role in modulating the expression of transcripts coding synaptic plasticity. We aim to investigate whether lead exposure affects UCP2 and hnRNP K expression levels. The Sprague-Dawley rats were exposed to different lead acetate concentrations (0 g/l, 0...
2021: Journal of environmental science and health. Part C, Toxicology and carcinogenesis
#55
JOURNAL ARTICLE
Jeffrey D Levengood, Jake Peterson, Blanton S Tolbert, Julien Roche
We have investigated the pressure- and temperature-induced conformational changes associated with the low complexity domain of hnRNP A1, an RNA-binding protein able to phase separate in response to cellular stress. Solution NMR spectra of the hnRNP A1 low-complexity domain fused with protein-G B1 domain were collected from 1 to 2,500 bar and from 268 K to 290 K. While the GB1 domain shows the typical pressure-induced and cold temperature-induced unfolding expected for small globular domains, the low-complexity domain of hnRNP A1 exhibits unusual pressure and temperature dependences...
February 6, 2021: Proteins
#56
JOURNAL ARTICLE
Annabella M Kolasa, Jasleen K Bhogal, Justin R DiAngelo
The availability of excess nutrients in Western diets has led to the overaccumulation of these nutrients as triglycerides, a condition known as obesity. The full complement of genes important for regulating triglyceride storage is not completely understood. Genome-wide RNAi screens in Drosophila cells have identified genes involved in mRNA splicing as important lipid storage regulators. Our lab has shown that a group of splicing factors called heterogeneous nuclear ribonucleoproteins (hnRNPs) regulate lipid metabolism in the fly fat body; however, the identities of all the hnRNPs that function to control triglyceride storage are not known...
March 2021: Biochemistry and Biophysics Reports
#57
JOURNAL ARTICLE
Elissa K Fultz, Michal A Coelho, Dylan Lieberman, C Leonardo Jimenez-Chavez, Camron D Bryant, Karen K Szumlinski
BACKGROUND: Hnrnph1 is a validated quantitative trait gene for methamphetamine behavioral sensitivity that encodes for heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1). This RNA-binding protein is involved in all stages of RNA metabolism that impacts mesocorticolimbic dopamine neurotransmission to influence addiction-related behavior. METHODS: We characterized the alcohol behavioral phenotypes of mice heterozygous for a deletion in the first coding exon of Hnrnph1 (Hnrnph1+/-)...
January 10, 2021: Drug and Alcohol Dependence
#58
JOURNAL ARTICLE
Xinyun Chen, Ying Liu, Chen Xu, Lina Ba, Zhuo Liu, Xiuya Li, Jie Huang, Ed Simpson, Hongyu Gao, Dayan Cao, Wei Sheng, Hanping Qi, Hongrui Ji, Maria Sanderson, Chen-Leng Cai, Xiaohui Li, Lei Yang, Jie Na, Kenichi Yamamura, Yunlong Liu, Guoying Huang, Weinian Shou, Ning Sun
The RNA-binding protein QKI belongs to the hnRNP K-homology domain protein family, a well-known regulator of pre-mRNA alternative splicing and is associated with several neurodevelopmental disorders. Qki is found highly expressed in developing and adult hearts. By employing the human embryonic stem cell (hESC) to cardiomyocyte differentiation system and generating QKI-deficient hESCs (hESCs-QKIdel ) using CRISPR/Cas9 gene editing technology, we analyze the physiological role of QKI in cardiomyocyte differentiation, maturation, and contractile function...
January 4, 2021: Nature Communications
#59
JOURNAL ARTICLE
Sabrina B Frederiksen, Lise L Holm, Martin R Larsen, Thomas K Doktor, Henriette S Andersen, Michelle L Hastings, Yimin Hua, Adrian R Krainer, Brage S Andresen
Understanding the splicing code can be challenging as several splicing factors bind to many splicing-regulatory elements. The SMN1 and SMN2 silencer element ISS-N1 is the target of the antisense oligonucleotide drug, Spinraza, which is the treatment against spinal muscular atrophy. However, limited knowledge about the nature of the splicing factors that bind to ISS-N1 and inhibit splicing exists. It is likely that the effect of Spinraza comes from blocking binding of these factors, but so far, an unbiased characterization has not been performed and only members of the hnRNP A1/A2 family have been identified by Western blot analysis and nuclear magnetic resonance to bind to this silencer...
December 10, 2020: Human Mutation
#60
JOURNAL ARTICLE
Matthew G Thompson, Mark Dittmar, Michael J Mallory, Prasanna Bhat, Max B Ferretti, Beatriz Ma Fontoura, Sara Cherry, Kristen W Lynch
Viral infection induces the expression of numerous host genes that impact the outcome of infection. Here we show that infection of human lung epithelial cells with Influenza A virus (IAV) also induces a broad program of alternative splicing of host genes. While these splicing-regulated genes are not enriched for canonical regulators of viral infection, we find that many of these genes do impact replication of IAV. Moreover, in several cases, specific inhibition of the IAV-induced splicing pattern also attenuates viral infection...
December 3, 2020: ELife
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