Functional Analysis of Genetic Variants and Somatic Mutations Impacting MicroRNA-Target Recognition: Bioinformatics Resources

2019 ◽  
pp. 101-120 ◽  
Author(s):  
Jesse D. Ziebarth ◽  
Anindya Bhattacharya ◽  
Yan Cui
Keyword(s):  
Functional Analysis ◽  
Genetic Variants ◽  
Somatic Mutations ◽  
Target Recognition ◽  
Microrna Target

Functional analysis of differences in transcriptional activity conferred by genetic variants in the 5′ flanking region of the IL12RB2 gene

2015 ◽  
Vol 68 (1) ◽  
pp. 55-65 ◽  
Author(s):  
Nahoko Kato-Kogoe ◽  
Hideki Ohyama ◽  
Soichiro Okano ◽  
Koji Yamanegi ◽  
Naoko Yamada ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Genetic Variants ◽  
Transcriptional Activity ◽  
Flanking Region

scholarly journals Genetic Variants in microRNA Target Sites of 37 Selected Cancer-Related Genes and the Risk of Cervical Cancer

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e86061 ◽  
Author(s):  
Yang Mi ◽  
Lijuan Wang ◽  
Lu Zong ◽  
Meili Pei ◽  
Qingyang Lu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Genetic Variants ◽  
Microrna Target ◽  
Target Sites

scholarly journals An alternative mode of microRNA target recognition

2012 ◽  
Vol 19 (3) ◽  
pp. 321-327 ◽  
Author(s):  
Sung Wook Chi ◽  
Gregory J Hannon ◽  
Robert B Darnell
Keyword(s):  
Target Recognition ◽  
Microrna Target ◽  
Alternative Mode

scholarly journals Contribution of clonal hematopoiesis to adult-onset hemophagocytic lymphohistiocytosis

Blood ◽  
2020 ◽  
Vol 136 (26) ◽  
pp. 3051-3055
Author(s):  
Peter G. Miller ◽  
Adam S. Sperling ◽  
Christopher J. Gibson ◽  
Kaushik Viswanathan ◽  
Cecilia Castellano ◽  
...  
Keyword(s):  
Older Adults ◽  
Mouse Model ◽  
Genetic Variants ◽  
Blood Cells ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Somatic Mutations ◽  
Adult Onset ◽  
Clonal Hematopoiesis ◽  
Inflammatory State ◽  
Life Threatening

Abstract Adult-onset hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease of immune hyperactivation. Unlike pediatric HLH, adult HLH is rarely driven by germline genetic variants. Although numerous precipitating etiologies have been identified, the reason that HLH occurs in only a subset of individuals and how other factors contribute to the disease remains unknown. We hypothesized that clonal hematopoiesis (CH), a state in which somatic mutations in blood cells cause an expanded population of mutant hematopoietic cells and drive an aberrant inflammatory state, could contribute to adult-onset HLH. In a highly annotated cohort of older adults with HLH we found that CH was more prevalent than in control cohorts. Using the adult-onset HLH mouse model in which repeated treatments of the TLR9 agonist, ODN1826, was delivered to the mouse, we observed that macrophages carrying mutations in Tet2, one of the most commonly mutated genes in CH, have an enhanced inflammatory response to TLR9 agonism. Finally, mice carrying Tet2 mutations in the hematopoietic compartment (a common model for CH) displayed an exaggerated response to TLR9 agonism, including worse splenomegaly and anemia. Our data suggest that CH is more common in individuals with adult-onset HLH and can contribute to the pathophysiology of this disease.

scholarly journals Molecular effects of cancer-associated somatic mutations on the structural and target recognition properties of Keap1

2015 ◽  
Vol 467 (1) ◽  
pp. 141-151 ◽  
Author(s):  
Halema Khan ◽  
Ryan C. Killoran ◽  
Anne Brickenden ◽  
Jingsong Fan ◽  
Daiwen Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Somatic Mutations ◽  
Target Recognition ◽  
Titration Calorimetry ◽  
Related Factor ◽  
Cancer Pathogenesis ◽  
Stress Response Pathway ◽  
Cytoprotective Enzymes ◽  
Molecular Effects ◽  
Target Binding

Kelch-like ECH-associated protein 1 (Keap1) plays an important regulatory role in the nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent oxidative stress response pathway. It functions as a repressor of Nrf2, a key transcription factor that initiates the expression of cytoprotective enzymes during oxidative stress to protect cells from damage caused by reactive oxygen species. Recent studies show that mutations of Keap1 can lead to aberrant activation of the antioxidant pathway, which is associated with different types of cancers. To gain a mechanistic understanding of the links between Keap1 mutations and cancer pathogenesis, we have investigated the molecular effects of a series of mutations (G333C, G350S, G364C, G379D, R413L, R415G, A427V, G430C and G476R) on the structural and target recognition properties of Keap1 by using nuclear magnetic resonance (NMR) spectroscopy, circular dichroism (CD) and isothermal titration calorimetry (ITC). Depending on their locations in the protein, these mutations are found to exert differential effects on the protein stability and target binding. Together with the proposed hinge-and-latch mechanism of Nrf2–Keap1 binding in the literature, our results provide important insight into the molecular affect of different somatic mutations on Keap1’s function as an Nrf2 repressor.

The role of site accessibility in microRNA target recognition

2007 ◽  
Vol 39 (10) ◽  
pp. 1278-1284 ◽  
Author(s):  
Michael Kertesz ◽  
Nicola Iovino ◽  
Ulrich Unnerstall ◽  
Ulrike Gaul ◽  
Eran Segal
Keyword(s):  
Target Recognition ◽  
Microrna Target

scholarly journals A structural view of microRNA–target recognition

2016 ◽  
Vol 44 (9) ◽  
pp. e82-e82 ◽  
Author(s):  
Guido Leoni ◽  
Anna Tramontano
Keyword(s):  
Target Recognition ◽  
Microrna Target

scholarly journals The power of multiplexed functional analysis of genetic variants

2016 ◽  
Vol 11 (10) ◽  
pp. 1782-1787 ◽  
Author(s):  
Molly Gasperini ◽  
Lea Starita ◽  
Jay Shendure
Keyword(s):  
Functional Analysis ◽  
Genetic Variants

scholarly journals Principles of MicroRNA–Target Recognition

PLoS Biology ◽  
2005 ◽  
Vol 3 (3) ◽  
pp. e85 ◽  
Author(s):  
Julius Brennecke ◽  
Alexander Stark ◽  
Robert B Russell ◽  
Stephen M Cohen
Keyword(s):  
Target Recognition ◽  
Microrna Target
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