Joanna Miskiewicz

Bio: Joanna Miskiewicz is an academic researcher from Poznań University of Technology. The author has contributed to research in topics: Protein Data Bank & Genotype. The author has an hindex of 3, co-authored 5 publications receiving 35 citations.

Bioinformatics Study of Structural Patterns in Plant MicroRNA Precursors.

Abstract: According to the RNA world theory, RNAs which stored genetic information and catalyzed chemical reactions had their contribution in the formation of current living organisms. In recent years, researchers studied this molecule diversity, i.a. focusing on small non-coding regulatory RNAs. Among them, of particular interest is evolutionarily ancient, 19–24 nt molecule of microRNA (miRNA). It has been already recognized as a regulator of gene expression in eukaryotes. In plants, miRNA plays a key role in the response to stress conditions and it participates in the process of growth and development. MicroRNAs originate from primary transcripts (pri-miRNA) encoded in the nuclear genome. They are processed from single-stranded stem-loop RNA precursors containing hairpin structures. While the mechanism of mature miRNA production in animals is better understood, its biogenesis in plants remains less clear. Herein, we present the results of bioinformatics analysis aimed at discovering how plant microRNAs are recognized within their precursors (pre-miRNAs). The study has been focused on sequential and structural motif identification in the neighbourhood of microRNA.

Topology-based classification of tetrads and quadruplex structures.

Abstract: MOTIVATION Quadruplexes attract the attention of researchers from many fields of bio-science. Due to a specific structure, these tertiary motifs are involved in various biological processes. They are also promising therapeutic targets in many strategies of drug development, including anticancer and neurological disease treatment. The uniqueness and diversity of their forms cause that quadruplexes show great potential in novel biological applications. The existing approaches for quadruplex analysis are based on sequence or 3D structure features and address canonical motifs only. RESULTS In our study, we analyzed tetrads and quadruplexes contained in nucleic acid molecules deposited in Protein Data Bank. Focusing on their secondary structure topology, we adjusted its graphical diagram and proposed new dot-bracket and arc representations. We defined the novel classification of these motifs. It can handle both canonical and non-canonical cases. Based on this new taxonomy, we implemented a method that automatically recognizes the types of tetrads and quadruplexes occurring as unimolecular structures. Finally, we conducted a statistical analysis of these motifs found in experimentally determined nucleic acid structures in relation to the new classification. AVAILABILITY AND IMPLEMENTATION https://github.com/tzok/eltetrado/. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

Discovering Structural Motifs in miRNA Precursors from the Viridiplantae Kingdom.

Abstract: A small non-coding molecule of microRNA (19⁻24 nt) controls almost every biological process, including cellular and physiological, of various organisms’ lives. The amount of microRNA (miRNA) produced within an organism is highly correlated to the organism’s key processes, and determines whether the system works properly or not. A crucial factor in plant biogenesis of miRNA is the Dicer Like 1 (DCL1) enzyme. Its responsibility is to perform the cleavages in the miRNA maturation process. Despite everything we already know about the last phase of plant miRNA creation, recognition of miRNA by DCL1 in pre-miRNA structures of plants remains an enigma. Herein, we present a bioinformatic procedure we have followed to discover structure patterns that could guide DCL1 to perform a cleavage in front of or behind an miRNA:miRNA* duplex. The patterns in the closest vicinity of microRNA are searched, within pre-miRNA sequences, as well as secondary and tertiary structures. The dataset consists of structures of plant pre-miRNA from the Viridiplantae kingdom. The results confirm our previous observations based on Arabidopsis thaliana precursor analysis. Hereby, our hypothesis was tested on pre-miRNAs, collected from the miRBase database to show secondary structure patterns of small symmetric internal loops 1-1 and 2-2 at a 1⁻10 nt distance from the miRNA:miRNA* duplex.

How bioinformatics resources work with G4 RNAs.

Abstract: Quadruplexes (G4s) are of interest, which increases with the number of identified G4 structures and knowledge about their biomedical potential. These unique motifs form in many organisms, including humans, where their appearance correlates with various diseases. Scientists store and analyze quadruplexes using recently developed bioinformatic tools-many of them focused on DNA structures. With an expanding collection of G4 RNAs, we check how existing tools deal with them. We review all available bioinformatics resources dedicated to quadruplexes and examine their usefulness in G4 RNA analysis. We distinguish the following subsets of resources: databases, tools to predict putative quadruplex sequences, tools to predict secondary structure with quadruplexes and tools to analyze and visualize quadruplex structures. We share the results obtained from processing specially created RNA datasets with these tools. Contact: mszachniuk@cs.put.poznan.pl Supplementary information: Supplementary data are available at Briefings in Bioinformatics online.

In Vitro and in Silico Analysis of miR-125a with rs12976445 Polymorphism in Breast Cancer Patients

Abstract: Background: Breast cancer affects over 2 million women yearly. Its early detection allows for successful treatment, which motivates to research factors that enable an accurate diagnosis. miR-125a is one of them, correlating with different types of cancer. For example, the miR-125a level decreases in breast cancer tissues; polymorphisms in the miR-125a encoding gene are related to prostate cancer and the risk of radiotherapy-induced pneumonitis. Methods: In this work, we investigated two variants of rs12976445 polymorphism in the context of breast cancer. We analyzed the data of 175 blood samples from breast cancer patients and compared them with the control data from 129 control samples. Results: We observed the tendency that in breast cancer cases TT genotype appeared slightly more frequent over CC and CT genotypes (statistically nonsignificant). The TT genotype appeared also to be more frequent among human epidermal growth factor receptor 2 (HER2) positive patients, compared to HER2 negative. In silico modelling showed that the presence of uridine (U) diminished the probability of pri-miR-125a binding to NOVA1 and HNRNPK proteins. We demonstrated that U and C -variants could promote different RNA folding patterns and provoke alternative protein binding. Conclusions: U-variant may imply a lower miR-125a expression in breast cancer.

MicroRNAs: Target Recognition and Regulatory Functions

Abstract: MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

Twenty years on.

Abstract: One of the problems of moving to the USA to practise medicine is taking \"finals\" again. I don't mean the exam for an Educational Council for Foreign Medical Graduates (ECFMG) certificate, which is a one-day affair taken in the familiar surroundings of London or Edinburgh. Without the ECFMG, of course, one's chances of getting a visa to live in the USA are next to nil. But actually to practise as an independent and fully functioning doctor something more extensive is demanded. One can sit these further tests only after burning one's boats, migrating to the USA, and risking all on the three-day \"trial.\" Each State has its own regulations but all, except Alaska and Florida, take a satisfactory performance in the Federation Licensing Examination (FLEX) held only in the USA as evidence of competence. Unlike Britain, where the MB ChB degrees or royal college diplomas are themselves registerable as evidence of competence, the MD degree in the USA does not give automatic entry into the ranks of practising doctors. In addition to having the MD a newly graduated doctor has to be successful in a three-part National Board of Medical Examiners (NBME) examination or FLEX, the latter having strong clinical emphasis in each of its three parts. Usually the NBME is taken by native US graduates and FLEX is favoured by the many foreign medical graduates who come to the USA to find fortune if not fame. The FLEX is extremely thorough and lasts three days, starting at 0830 and ending at 1730 with an hour for lunch and one 15-minute break during the morning and afternoon sessions. I took the exam at the beginning of December 1975 at the McCormick Place Centre in Chicago, which is a huge, draughty, hanger-like exhibition hall overlooking Lake Michigan and Meigs Field aerodrome. The 500-odd candidates were a colourfully international crowd with only a few from Britain. The place was so cold that most people sat in their overcoats and the proctors refreshed themselves at frequent intervals from hot vacuum flasks.

The Critical Role of miRNAs in Regulation of Flowering Time and Flower Development.

Abstract: Flowering is an important biological process for plants that ensures reproductive success. The onset of flowering needs to be coordinated with an appropriate time of year, which requires tight control of gene expression acting in concert to form a regulatory network. MicroRNAs (miRNAs) are non-coding RNAs known as master modulators of gene expression at the post-transcriptional level. Many different miRNA families are involved in flowering-related processes such as the induction of floral competence, floral patterning, and the development of floral organs. This review highlights the diverse roles of miRNAs in controlling the flowering process and flower development, in combination with potential biotechnological applications for miRNAs implicated in flower regulation.

RNA-Puzzles toolkit: a computational resource of RNA 3D structure benchmark datasets, structure manipulation, and evaluation tools.

Abstract: Significant improvements have been made in the efficiency and accuracy of RNA 3D structure prediction methods during the succeeding challenges of RNA-Puzzles, a community-wide effort on the assessment of blind prediction of RNA tertiary structures. The RNA-Puzzles contest has shown, among others, that the development and validation of computational methods for RNA fold prediction strongly depend on the benchmark datasets and the structure comparison algorithms. Yet, there has been no systematic benchmark set or decoy structures available for the 3D structure prediction of RNA, hindering the standardization of comparative tests in the modeling of RNA structure. Furthermore, there has not been a unified set of tools that allows deep and complete RNA structure analysis, and at the same time, that is easy to use. Here, we present RNA-Puzzles toolkit, a computational resource including (i) decoy sets generated by different RNA 3D structure prediction methods (raw, for-evaluation and standardized datasets), (ii) 3D structure normalization, analysis, manipulation, visualization tools (RNA_format, RNA_normalizer, rna-tools) and (iii) 3D structure comparison metric tools (RNAQUA, MCQ4Structures). This resource provides a full list of computational tools as well as a standard RNA 3D structure prediction assessment protocol for the community.

The Menu of Features that Define Primary MicroRNAs and Enable De Novo Design of MicroRNA Genes

Abstract: MicroRNAs (miRNAs) are small regulatory RNAs processed from stem-loop regions of primary transcripts (pri-miRNAs), with the choice of stem loops for initial processing largely determining what becomes a miRNA. To identify sequence and structural features influencing this choice, we determined cleavage efficiencies of >50,000 variants of three human pri-miRNAs, focusing on the regions intractable to previous high-throughput analyses. Our analyses revealed a mismatched motif in the basal stem region, a preference for maintaining or improving base pairing throughout the remainder of the stem, and a narrow stem-length preference of 35 ± 1 base pairs. Incorporating these features with previously identified features, including three primary-sequence motifs, yielded a unifying model defining mammalian pri-miRNAs in which motifs help orient processing and increase efficiency, with the presence of more motifs compensating for structural defects. This model enables generation of artificial pri-miRNAs, designed de novo, without reference to any natural sequence yet processed more efficiently than natural pri-miRNAs.