The Role of Tertiary Structure in MicroRNA Target Recognition

Author(s):  
Hin Hark Gan ◽  
Kristin C. Gunsalus
2007 ◽  
Vol 39 (10) ◽  
pp. 1278-1284 ◽  
Author(s):  
Michael Kertesz ◽  
Nicola Iovino ◽  
Ulrich Unnerstall ◽  
Ulrike Gaul ◽  
Eran Segal

2020 ◽  
Vol 17 (2) ◽  
pp. 125-132
Author(s):  
Marjanu Hikmah Elias ◽  
Noraziah Nordin ◽  
Nazefah Abdul Hamid

Background: Chronic Myeloid Leukaemia (CML) is associated with the BCRABL1 gene, which plays a central role in the pathogenesis of CML. Thus, it is crucial to suppress the expression of BCR-ABL1 in the treatment of CML. MicroRNA is known to be a gene expression regulator and is thus a good candidate for molecularly targeted therapy for CML. Objective: This study aims to identify the microRNAs from edible plants targeting the 3’ Untranslated Region (3’UTR) of BCR-ABL1. Methods: In this in silico analysis, the sequence of 3’UTR of BCR-ABL1 was obtained from Ensembl Genome Browser. PsRNATarget Analysis Server and MicroRNA Target Prediction (miRTar) Server were used to identify miRNAs that have binding conformity with 3’UTR of BCR-ABL1. The MiRBase database was used to validate the species of plants expressing the miRNAs. The RNAfold web server and RNA COMPOSER were used for secondary and tertiary structure prediction, respectively. Results: In silico analyses revealed that cpa-miR8154, csi-miR3952, gma-miR4414-5p, mdm-miR482c, osa-miR1858a and osa-miR1858b show binding conformity with strong molecular interaction towards 3’UTR region of BCR-ABL1. However, only cpa-miR- 8154, osa-miR-1858a and osa-miR-1858b showed good target site accessibility. Conclusion: It is predicted that these microRNAs post-transcriptionally inhibit the BCRABL1 gene and thus could be a potential molecular targeted therapy for CML. However, further studies involving in vitro, in vivo and functional analyses need to be carried out to determine the ability of these miRNAs to form the basis for targeted therapy for CML.


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

FEBS Journal ◽  
2007 ◽  
Vol 274 (23) ◽  
pp. 6167-6179 ◽  
Author(s):  
Roberta Chiaraluce ◽  
Rita Florio ◽  
Sebastiana Angelaccio ◽  
Giulio Gianese ◽  
Johan F. T. van Lieshout ◽  
...  

Biochemistry ◽  
1997 ◽  
Vol 36 (14) ◽  
pp. 4309-4316 ◽  
Author(s):  
Shin-ya Ohki ◽  
Mitsuhiko Ikura ◽  
Mingjie Zhang

FEBS Journal ◽  
2007 ◽  
Vol 0 (0) ◽  
pp. 071115064009001-???
Author(s):  
Roberta Chiaraluce ◽  
Rita Florio ◽  
Sebastiana Angelaccio ◽  
Giulio Gianese ◽  
Johan F. T. van Lieshout ◽  
...  

2020 ◽  
Vol 21 (12) ◽  
pp. 4567 ◽  
Author(s):  
Hannah E. Zenker ◽  
Malgorzata Teodorowicz ◽  
Arifa Ewaz ◽  
R.J. Joost van Neerven ◽  
Huub F.J. Savelkoul ◽  
...  

Intake of dietary advanced glycation end products (AGEs) is associated with inflammation-related health problems. Nε-carboxymethyl lysine (CML) is one of the best characterised AGEs in processed food. AGEs have been described as ligands for receptors present on antigen presenting cells. However, changes in protein secondary and tertiary structure also induce binding to AGE receptors. We aimed to discriminate the role of different protein modifications in binding to AGE receptors. Therefore, β-lactoglobulin was chemically modified with glyoxylic acid to produce CML and compared to β-lactoglobulin glycated with lactose. Secondary structure was monitored with circular dichroism, while hydrophobicity and formation of β-sheet structures was measured with ANS-assay and ThT-assay, respectively. Aggregation was monitored using native-PAGE. Binding to sRAGE, CD36, and galectin-3 was measured using inhibition ELISA. Even though no changes in secondary structure were observed in all tested samples, binding to AGE receptors increased with CML concentration of CML-modified β-lactoglobulin. The negative charge of CML was a crucial determinant for the binding of protein bound CML, while binding of glycated BLG was determined by increasing hydrophobicity. This shows that sRAGE, galectin-3, and CD36 bind to protein bound CML and points out the role of negatively charged AGEs in binding to AGE receptors.


Plants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 141 ◽  
Author(s):  
Muhammad Shahbaz ◽  
Marinus Pilon

Copper (Cu) is a micronutrient for plants. Three small RNAs, which are up-regulated by Cu deficiency and target transcripts for Cu proteins, are among the most conserved microRNAs in plants. It was hypothesized that these Cu-microRNAs help save Cu for the most essential Cu-proteins under deficiency. Testing this hypothesis has been a challenge due to the redundancy of the Cu microRNAs and the properties of the regulatory circuits that control Cu homeostasis. In order to investigate the role of Cu-microRNAs in Cu homeostasis during vegetative growth, we used a tandem target mimicry strategy to simultaneously inhibit the function of three conserved Cu-microRNAs in Arabidopsis thaliana. When compared to wild-type, transgenic lines that express the tandem target mimicry construct showed reduced Cu-microRNA accumulation and increased accumulation of transcripts that encode Cu proteins. As a result, these mimicry lines showed impaired photosynthesis and growth compared to wild type on low Cu, which could be ascribed to a defect in accumulation of plastocyanin, a Cu-containing photosynthetic electron carrier, which is itself not a Cu-microRNA target. These data provide experimental support for a Cu economy model where the Cu-microRNAs together function to allow maturation of essential Cu proteins under impending deficiency.


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