Κατεύθυνση Βιοπληροφορική
Πληροφορική

2017-03-21

2017

Kakoulidis Panagiotis

Άρτεμις Χατζηγεωργίου, Καθηγήτρια, Τμήμα Μηχανικών Η/Υ Τηλεπικοινωνιών και Δικτύων, Πανεπιστήμιο Θεσσαλίας

Development of a pipeline for secondary and tertiary structural analysis of human miRNA targeting

English
Greek

Development of a pipeline for secondary and tertiary structural analysis of human miRNA targeting

The majority of current miRNA-targeting studies do not take into account the tertiary
structures of RNA and Argonaute-2 (AGO2) protein. Target3D (pronounced "targeted")
pipeline was developed following the advancements in the emerging field of the RNA
three-dimensional structure prediction along with the growing availability of high quality
experimental crystal structures of RNAs and human AGO2-miRNA-mRNA complexes.
The pipeline yields structural information from the sequences of the miRNA-mRNA
duplex. Secondary structural motifs are identified in two selected RNA segments; one
segment of the target mRNA where miRNA Recognition Elements (MRE) reside and
one that encloses the interacting area of miRNA. The three dimensional structural
model of the mRNA segment is produced via simulation and homology modelling. It is a
representation of the MRE area in an unbound state. A fragment representing the
bound state is extracted from a experimentally derived structural model of the ternary
complex (AGO2-miRNA-mRNA), which is used as a reference structure. The two
fragments are compared for their structural similarity through the calculation of a metric,
which is an adapted version of TM-Score. The aforementioned reference structure has
undergone a thorough refinement process and it gets further modified to match the
sequences in study during the pipeline's execution. Part of the modification is the
energy minimization which is performed with a force field that was customized to fit the
purposes of the pipeline. The resulting structure is suitable for further Molecular
Dynamics study and visualization. Moreover, the software identifies intermolecular and
interatomic interactions between human AGO2 protein, guide miRNA and target mRNA.

Health Sciences

microRNA, miRNA, tertiary structure, secondary structure, RNA Sequencing, Molecular Dynamics, Argonaute 2, RISC, MRE, mRNA, molecular interface, energy minimization, force field parameterization, homology modeling

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https://pergamos.lib.uoa.gr/uoa/dl/object/1387544