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Jung-Chun Lin
Alternative splicing has been widely demonstrated to function as pivotal regulation in specifying cellular fates and biological functions. The relative expression or cellular localization of a splicing factor constitutes an important mechanism in spatiotemporal programming of cell- and stage-specific splicing profiles. In this study, results of deep RNA-sequencing (RNA-Seq) analyses first revealed the reprogrammed splicing profile and reduced expression of serine/arginine-rich splicing factor protein kinase 1 (SRPK1) throughout the development of brown adipose tissue (BAT)...
February 20, 2018: Biochimica et Biophysica Acta
Vincenzo A Gennarino, Elizabeth E Palmer, Laura M McDonell, Li Wang, Carolyn J Adamski, Amanda Koire, Lauren See, Chun-An Chen, Christian P Schaaf, Jill A Rosenfeld, Jessica A Panzer, Ute Moog, Shuang Hao, Ann Bye, Edwin P Kirk, Pawel Stankiewicz, Amy M Breman, Arran McBride, Tejaswi Kandula, Holly A Dubbs, Rebecca Macintosh, Michael Cardamone, Ying Zhu, Kevin Ying, Kerith-Rae Dias, Megan T Cho, Lindsay B Henderson, Berivan Baskin, Paula Morris, Jiang Tao, Mark J Cowley, Marcel E Dinger, Tony Roscioli, Oana Caluseriu, Oksana Suchowersky, Rani K Sachdev, Olivier Lichtarge, Jianrong Tang, Kym M Boycott, J Lloyd Holder, Huda Y Zoghbi
Certain mutations can cause proteins to accumulate in neurons, leading to neurodegeneration. We recently showed, however, that upregulation of a wild-type protein, Ataxin1, caused by haploinsufficiency of its repressor, the RNA-binding protein Pumilio1 (PUM1), also causes neurodegeneration in mice. We therefore searched for human patients with PUM1 mutations. We identified eleven individuals with either PUM1 deletions or de novo missense variants who suffer a developmental syndrome (Pumilio1-associated developmental disability, ataxia, and seizure; PADDAS)...
February 22, 2018: Cell
Haiyang Hu, Jian-Mei Liu, Zhenyu Hu, Xi Jiang, Xiaode Yang, Jiangxia Li, Yao Zhang, Haijing Yu, Philipp Khaitovich
MicroRNA (miRNA) sponges are vital components of posttranscriptional gene regulation. Yet, only a limited number of miRNA sponges have been identified. Here, we show that the recently evolved non-coding tumor suppressor transcript, antisense RNA to TP73 gene (TP73-AS1), functions as a natural sponge of human-specific miRNA miR-941. We find unusually nine high-affinity miR-941 binding sites clustering within 1kb region on TP73-AS1, which forms miR-941 sponge region. This sponge region displays increased sequence constraint only in humans, and its formation can be traced to the tandem expansion of a 71-nt-long sequence containing a single miR-941 binding site in old world monkeys...
February 20, 2018: Molecular Biology and Evolution
Andreas B Gevaert, Isabel Witvrouwen, Christiaan J Vrints, Hein Heidbuchel, Emeline M Van Craenenbroeck, Steven J Van Laere, Amaryllis H Van Craenenbroeck
MicroRNA (miRNA) regulate gene expression through posttranscriptional mRNA degradation or suppression of translation. Many (pre)analytical issues remain to be resolved for miRNA screening with TaqMan Low Density Arrays (TLDA) in plasma samples, such as optimal RNA isolation, preamplification and data normalization. We optimized the TLDA protocol using three RNA isolation protocols and preamplification dilutions. By using 100μL elution volume during RNA isolation and adding a preamplification step without dilution, 49% of wells were amplified...
2018: PloS One
Yong Mao, Chengda Zou, Fanyi Meng, Jiehong Kong, Weipeng Wang, Dong Hua
The single nucleotide polymorphisms (SNPs) in the microRNA precursor (pre-miRNA) may modulate the posttranscriptional regulation of gene expression and explain individual sensitivity to chemotherapy. Here we investigated the correlation between 23 SNPs in the pre-miRNA and the efficacy of capecitabine-based chemotherapy in 274 advanced colon cancer patients. Statistical analysis indicated that much more patients with rs744591 A/C(48.03%), C/C (53.45%) or C allele (49.73%) responded to the chemotherapy than those with the A/A genotype (33...
January 23, 2018: Oncotarget
John J Brewington, Jessica Backstrom, Amanda Feldman, Elizabeth L Kramer, Jessica D Moncivaiz, Alicia J Ostmann, Xiaoting Zhu, L Jason Lu, John P Clancy
Traditional pulmonary therapies for cystic fibrosis (CF) target the downstream effects of CF transmembrane conductance regulator (CFTR) dysfunction (the cause of CF). Use of one such therapy, β-adrenergic bronchodilators (such as albuterol), is nearly universal for airway clearance. Conversely, novel modulator therapies restore function to select mutant CFTR proteins, offering a disease-modifying treatment. Recent trials of modulators targeting F508del-CFTR, the most common CFTR mutation, suggest that chronic β-agonist use may undermine clinical modulator benefits...
February 22, 2018: JCI Insight
Agnieszka Dzikiewicz-Krawczyk, Arjan Diepstra, Bea Rutgers, Gertrud Kortman, Debora de Jong, Jasper Koerts, Marian Bulthuis, Tineke van der Sluis, Annika Seitz, Lydia Visser, Klaas Kok, Joost Kluiver, Anke van den Berg
MicroRNAs (miRNAs) are small noncoding RNAs involved in the posttranscriptional regulation of gene expression. Deregulated miRNA levels have been linked to Burkitt lymphoma (BL) pathogenesis. To date, the number of known pathogenesis-related miRNA-target gene interactions is limited. Here, we determined for the first time the miRNA targetomes of primary BL tumors and normal B cells. AGO2-RNA immunoprecipitation (AGO2-RIP) of two frozen diagnostic BL tissue samples and three CD19+ B-cell samples isolated from routinely removed tonsils revealed distinct miRNA targetomes of BL and normal B cells...
February 16, 2018: American Journal of Pathology
Jonathan R Brody, Dan A Dixon
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with dismal patient outcomes. The underlying core genetic drivers of disease have been identified in human tumor specimens and described in genetically engineered mouse models. These genetic drivers of PDAC include KRAS signaling, TP53 mutations, and genetic loss of the SMAD4 tumor suppressor protein. Beyond the known mutational landscape of PDAC genomes, alternative disrupted targets that extend beyond conventional genetic mutations have been elusive and understudied in the context of PDAC cell therapeutic resistance and survival...
February 16, 2018: Wiley Interdisciplinary Reviews. RNA
Hervé Seligmann, Didier Raoult
We examine the hypothesis that de novo template-free RNAs still form spontaneously, as they did at the origins of life, invade modern genomes, contribute new genetic material. Previously, analyses of RNA secondary structures suggested that some RNAs resembling ancestral (t)RNAs formed recently de novo , other parasitic sequences cluster with rRNAs. Here positive control analyses of additional RNA secondary structures confirm ancestral and de novo statuses of RNA grouped according to secondary structure. Viroids with branched stems resemble de novo RNAs, rod-shaped viroids resemble rRNA secondary structures, independently of GC contents...
2018: Frontiers in Microbiology
Keli L Hippen, Michael Loschi, Jemma Nicholls, Kelli P A MacDonald, Bruce R Blazar
Regulatory T cells (Tregs) are key mediators of the immune system. MicroRNAs (miRNAs) are a family of ~22 nucleotide non-coding RNAs that are processed from longer precursors by the RNases Drosha and Dicer. miRNA regulates protein expression posttranscriptionally through mRNA destabilization or translational silencing. A critical role for miRNA in Treg function was initially discovered when both Dicer and Drosha knockout (KO) mice were found to develop a fatal autoimmune disease phenotypically similar to Foxp3 KO mice...
2018: Frontiers in Immunology
Jiao Li, Wenchen Pu, Hui-Lung Sun, Jian-Kang Zhou, Xin Fan, Yuanyuan Zheng, Juan He, Xuesha Liu, Zhichu Xia, Lunxu Liu, Yu-Quan Wei, Yong Peng
MicroRNA (miRNA) dysregulation is associated with the tumorigenesis and development of numerous human cancers. The defect in miRNA biogenesis is the main cause of miRNA dysregulation. We previously demonstrated that ERK-induced phosphorylation of XPO5 followed by peptidyl-prolyl cis/trans isomerase Pin1-mediated isomerization downregulates miRNA expression and contributes to hepatocellular carcinoma (HCC) development. However, how Pin1 precisely regulates miRNA biogenesis in HCC remains elusive. Here we reveal that Pin1 has a pivotal role in the miRNA maturation process by modulating phosphorylated Serine-Proline (pS-P) motif of XPO5 in a phosphorylation-dependent manner...
February 14, 2018: Cell Death and Differentiation
Hui Shen, Yi Tian, Xiaolei Yao, Wen Liu, Yujin Zhang, Zhibo Yang
Psoriasis, a common chronic skin disorder, is characterized by hyperproliferation and aberrant differentiation of keratinocytes and infiltration of inflammatory cells into the dermis and epidermis. MicroRNAs (miRNAs) are a large family of highly conserved small non-coding RNA which regulates diverse biological process, including cell proliferation, by modulating gene expression at the posttranscriptional level. In the present study, we indicated that miR-99a was specifically downregulated in psoriatic dermatic lesions, and could inhibit HaCaT cells' proliferation; by direct targeting, miR-99a could also regulate the expression of Frizzled-5 (FZD5)/Frizzled-8 (FZD8)...
August 1, 2017: Die Pharmazie
Yuyu Li, Jiawei Zhang, Jie Pan, Xu Feng, Peipei Duan, Xing Yin, Yang Xu, Xin Wang, Shujuan Zou
Long noncoding RNAs (lncRNAs) are a class of non-protein-coding transcripts with the length longer than 200 nucleotides. Growing evidence suggests that lncRNAs, which were initially thought to be merely transcriptional "noise", participate in a wide repertoire of biological processes. It has been well established that lncRNAs not only play important roles in genomic regulation, transcription, posttranscriptional processes but are also implicated in the pathogenesis of human diseases including cardiovascular diseases, diabetes, neurodegenerative disorders, and cancer...
2018: Cell & Bioscience
Adrien Labriet, Eric P Allain, Michele Rouleau, Yannick Audet-Delage, Lyne Villeneuve, Chantal Guillemette
The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics. Preferred substrates possess tertiary aliphatic amines and heterocyclic amines such as tobacco carcinogens and several anti-depressants and anti-psychotics. We hypothesized that alternative splicing (AS) constitutes a mean to regulate steady state levels of UGT2B10 and enzyme activity. We established the transcriptome of UGT2B10 in normal and tumoral tissues of multiple individuals...
February 9, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Thomas Rohan, Kenny Ye, Yihong Wang, Andrew G Glass, Mindy Ginsberg, Olivier Loudig
MicroRNAs are endogenous, small non-coding RNAs that control gene expression by directing their target mRNAs for degradation and/or posttranscriptional repression. Abnormal expression of microRNAs is thought to contribute to the development and progression of cancer. A history of benign breast disease (BBD) is associated with increased risk of subsequent breast cancer. However, no large-scale study has examined the association between microRNA expression in BBD tissue and risk of subsequent invasive breast cancer (IBC)...
2018: PloS One
Jingkui Wang, Laura Symul, Jake Yeung, Cédric Gobet, Jonathan Sobel, Sarah Lück, Pål O Westermark, Nacho Molina, Felix Naef
The mammalian circadian clock coordinates physiology with environmental cycles through the regulation of daily oscillations of gene expression. Thousands of transcripts exhibit rhythmic accumulations across mouse tissues, as determined by the balance of their synthesis and degradation. While diurnally rhythmic transcription regulation is well studied and often thought to be the main factor generating rhythmic mRNA accumulation, the extent of rhythmic posttranscriptional regulation is debated, and the kinetic parameters (e...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Alok Kumar, Jai Prakash Jaiswal, Netrapal Sharma, Supriya Gupta, Anil Kumar
Increasing nutritional value of cereals is one of the important research and breeding objectives to overcome malnutrition in developing countries. The synthesis of grain seed proteins during grain filling is controlled by several mechanisms including transcriptional and posttranscriptional modifications. In the current investigation, transcript abundance analysis of three allelic variants of seed storage protein activator (Spa A, Spa B and Spa D) and NAM-B1 affecting seed nutrient concentration was carried out in two genotypes (UP 2672 and HS 540) of bread wheat differing in grain protein content...
February 2018: 3 Biotech
Zoltán Nagy, Ábel Decmann, Pál Perge, Péter Igaz
Adrenocortical tumours are quite prevalent. Most of these tumours are benign, hormonally inactive adrenocortical adenomas. Rare hormone-secreting adrenocortical adenomas are associated with severe clinical consequences, whereas the prognosis of the rare adrenocortical cancer is rather poor in its advanced stages. The pathogenesis of these tumours is only partly elucidated. MicroRNAs are small, non-coding RNA molecules that are pivotal in the regulation of several basic cell biological processes via the posttranscriptional regulation of gene expression...
February 2018: Orvosi Hetilap
Kinga Németh, Ottó Darvasi, Nikolette Szücs, Sándor Czirják, Henriett Butz
MicroRNAs (miRNAs) are short, single stranded RNA molecules which play regulatory roles through posttranscriptional regulation of their target genes. Based on our current knowledge, more than 30% of the human protein-coding genes are regulated by miRNAs, hence influencing basic cellular mechanisms including cell proliferation, differentiation and cell death. Differential miRNA expression pattern has been detected in many different types of tumors and, recently, several publications have referred to miRNAs as potential therapeutic targets...
February 2018: Orvosi Hetilap
X-H Liu, J Wang, Y-H Dong
OBJECTIVE: Sp1 is a member of super zinc finger structure family that participates in cancer cells' apoptosis, proliferation, survival, and differentiation. This study detected the expressions of miR-375 and sp1 in colorectal cancer tissue and cells to analyze their impact on cell proliferation. PATIENTS AND METHODS: Colorectal cancer patients in our hospital were enrolled. HCT-116 cell was transfected with miR-375 mimics, mimics control, and miR-375 + sp1, respectively...
January 2018: European Review for Medical and Pharmacological Sciences
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