A5039950251- Genetic Neurodegenerative Diseases
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- MicroRNA in disease regulation
- Mitochondrial Function and Pathology
- DNA Repair Mechanisms
- RNA Interference and Gene Delivery
- BRCA gene mutations in cancer
- CRISPR and Genetic Engineering
- Genomic variations and chromosomal abnormalities
- RNA regulation and disease
- Muscle Physiology and Disorders
- Cancer Genomics and Diagnostics
- Advanced biosensing and bioanalysis techniques
- Cancer-related molecular mechanisms research
- Nutrition, Genetics, and Disease
- Synthesis and Characterization of Heterocyclic Compounds
- Molecular Biology Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Neurogenetic and Muscular Disorders Research
- DNA and Nucleic Acid Chemistry
- Enzyme Structure and Function
- Viral Infections and Immunology Research
- Circular RNAs in diseases
Institute of Bioorganic Chemistry, Polish Academy of Sciences
2011-2021
Polish Academy of Sciences
2000-2015
University of Toronto
2012
Cancer Genetics (United States)
2011
Australian Nuclear Science and Technology Organisation
2008
The University of Sydney
2008
University of California, Los Angeles
2008
Institute of Biochemistry and Biophysics, Polish Academy of Sciences
2007
La Roche College
1988
Institute of Organic Chemistry
1978-1979
The CAG repeat expansions that occur in translated regions of specific genes can cause human genetic disorders known as polyglutamine (poly-Q)-triggered diseases. Huntington’s disease and spinobulbar muscular atrophy (SBMA) are examples these diseases which underlying mutations localized near other trinucleotide repeats the huntingtin (HTT) androgen receptor (AR) genes, respectively. Mutant proteins contain expanded tracts well-known triggers pathogenesis poly-Q diseases, but a toxic role...
We have established the structures of 10 human microRNA (miRNA) precursors using biochemical methods. Eight these turned out to be different from those that were computer-predicted. The differences localized in terminal loop region and at opposite side precursor hairpin stem. analyzed features perspectives miRNA biogenesis active strand selection. demonstrated thermodynamic stability profiles for pre-miRNA hairpins harboring miRNAs their 5′- 3′-sides discussed functional implications. Our...
The biogenesis of human microRNAs (miRNAs) includes two RNA cleavage steps in which the activities RNases Drosha and Dicer are involved. miRNAs diverse lengths generated from different genes, that heterogeneous length produced a single miRNA gene. We determined solution structures many precursors analysed structural basis diversity using new measure: weighted average diced (WALDI). found asymmetrical motifs present precursor hairpins primarily responsible for by Dicer. High-resolution...
Mutant transcripts containing expanded CUG repeats in the untranslated region are a pathogenic factor myotonic dystrophy type 1 (DM1). The mutant RNA sequesters muscleblind-like (MBNL1) splicing and causes misregulation of alternative multiple genes that linked to clinical symptoms disease. In this study, we show either long CAG repeat or short synthetic induce aberrations typical DM1. Alternative defects also caused by translated normal cells transfected with ATXN3 gene construct derived...
Trinucleotide repeats (TNRs) are of interest in genetics because they used as markers for tracing genotype–phenotype relations and directly involved numerous human genetic diseases. In this study, we searched the genome reference sequence annotated exons (exome) presence uninterrupted triplet repeat tracts composed six or more repeated units. A list 32 448 TNRs 878 TNR-containing genes was generated is provided herein. We found that some repeats, specifically CNG, overrepresented, while CTT,...
Tandem repeats of various trinucleotide motifs are present in the human transcriptome, but functions these regular sequences, which likely depend on structures they form, still poorly understood. To gain new insight into structural and functional properties triplet RNA, we have performed a biochemical analysis complete set repeat transcripts, each composed single sequence repeated 17 times. We show that transcripts fall four classes. The CAA, UUG, AAG, CUU, CCU, CCA, UAA did not form any...
One of the cellular functions ribonuclease Dicer is to process microRNA precursors (pre-miRNAs) into mature microRNAs (miRNAs). Human performs this function in cooperation with its protein partners, AGO2, PACT and TRBP. The exact role these accessory proteins activity still poorly understood. In study, we used northern blotting technique investigate pre-miRNA cleavage efficiency specificity after depletion TRBP by RNAi. results showed that inhibition either partner substantially affected not...
Huntington's disease (HD) is a progressive autosomal dominant neurodegenerative disorder caused by the expansion of CAG repeats in first exon huntingtin gene (HTT). The accumulation polyglutamine-rich proteins affects various cellular functions and causes selective degeneration neurons striatum. Therapeutic strategies used to date silence expression mutant HTT include antisense oligonucleotides, RNA interference-based approaches and, recently, genome editing with CRISPR/Cas9 system. Here, we...
We show that CUG repeats form "slippery" hairpins in their natural sequence context of the myotonin kinase gene transcript. This novel type RNA structure is characterized by strong S1 and T1 nuclease lead cleavages terminal loop mild hairpin stem. The latter effect indicates a relaxed metastable (CUG)5 do not any detectable secondary structure, whereas increasing stability are formed (CUG)11, (CUG)21, (CUG)49. potential role pathogenesis myotonic dystrophy discussed. Eleven human diseases...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIn vitro synthesis of 16S ribosomal RNA containing single base changes and assembly into a functional 30S ribosomeW. Krzyzosiak, R. Denman, K. Nurse, W. Hellmann, M. Boublik, C. Gehrke, P. F. Agris, J. OfengandCite this: Biochemistry 1987, 26, 8, 2353–2364Publication Date (Print):April 1, 1987Publication History Published online1 May 2002Published inissue 1 April...
Spinocerebellar ataxia type 2 (SCA2), one of the hereditary human neurodegenerative disorders, is caused by expansion CAG tandem repeats in translated sequence SCA2 gene. In a normal population repeat polymorphic not only length but also number and localization its CAA interruptions. The aim this study was to determine structure region mutant transcripts reveal structural basis function dysfunction. We show here that properties interruptions are major determinants folding transcripts....
CAG repeats occur predominantly in the coding regions of human genes, which suggests their functional importance. In some these sequences can undergo pathogenic expansions leading to neurodegenerative polyglutamine (poly-Q) diseases. The mutant transcripts containing expanded possibly contribute pathogenesis addition well-known effects proteins. We have analysed two crystal forms RNA duplexes repeats: (GGCAGCAGCC)2. One structures has been determined at atomic resolution (0.95 Å) and other...
Abstract Background Numerous microRNAs (miRNAs) have heterogeneous ends resulting from imprecise cleavages by processing nucleases and various non-templated nucleotide additions. The scale of miRNA end-heterogeneity is best shown deep sequencing data revealing not only the major variants but also those that occur in minute amounts are unlikely to be functional importance. All RNA interference (RNAi) technology reagents expressed processed cells exposed same machinery generating released...