Biomedical subjects

Mateusz de Mezer

Publications and source records attributed to Mateusz de Mezer.

4 recordsLinked to original sources

PubMed2005

Facile FMR1 mRNA structure regulation by interruptions in CGG repeats.

RNA metabolism is a major contributor to the pathogenesis of clinical disorders associated with premutation size alleles of the fragile X mental retardation (FMR1) gene. Herein, we determined the structural properties of numerous FMR1 transcripts harboring different numbers of both CGG repeats and AGG interruptions. The stability of hairpins formed by uninterrupted repeat-containing transcripts increased with the lengthening of the repeat tract. Even a single AGG interruption in the repeated sequence dramatically changed the folding of the 5'UTR fragments, typically resulting in branched hairpin structures. Transcripts containing different lengths of CGG repeats, but sharing a common AGG pattern, adopted similar types of secondary structures. We postulate that interruption-dependent structure variants of the FMR1 mRNA contribute to the phenotype diversity, observed in premutation carriers.

5' Untranslated Regions↗

PubMed2003

RNA structure of trinucleotide repeats associated with human neurological diseases.

The tandem repeats of trinucleotide sequences are present in many human genes and their expansion in specific genes causes a number of hereditary neurological disorders. The normal function of triplet repeats in transcripts is barely known and the role of expanded RNA repeats in the pathogenesis of Triplet Repeat Expansion Diseases needs to be more fully elucidated. Here we have described the structures formed by transcripts composed of AAG, CAG, CCG, CGG and CUG repeats, which were determined by chemical and enzymatic structure probing. With the exception of the repeated AAG motif, all studied repeats form hairpin structures and these hairpins show several alternative alignments. We have determined the molecular architectures of these co-existing hairpin structures by using transcripts with GC-clamps which imposed single alignments of hairpins. We have provided experimental evidence that CCUG repeats implicated in myotonic dystrophy type 2 also form hairpin structures with properties similar to that composed of the CUG repeats.

Base Sequence↗

PubMed2003

Structures of trinucleotide repeats in human transcripts and their functional implications.

Among the goals of RNA structural and functional genomics is determining structures and establishing the functions of a rich repertoire of simple sequence repeats in transcripts. These repeats are present in transcripts from their 'birth' in the nucleus to their 'death' in cytoplasm and have the potential of being involved in many steps of RNA regulation. The knowledge of their structural features and functional roles will also shed more light on the postulated mechanisms of RNA pathogenesis in a growing list of neurological diseases caused by simple sequence repeat expansions. Here, we discuss several different lines of research to support the hypothesis that the mechanism of RNA pathogenesis may be a more common phenomenon triggered or modulated also by abundant long normal repeats. We propose structures of the repeat regions in transcripts of genes involved in Triplet Repeat Expansion Diseases. We have classified the polymorphic repeat alleles of these genes according to their ability to form hairpin structures in transcripts, and describe the distribution of different structural forms of the repeats in the human population. We have also reported the results of a systematic survey of the human transcriptome to identify mRNAs containing triplet repeats and to classify them according to structural and functional criteria. Based on this knowledge, we discuss the putative wider role of triplet repeat RNA hairpins in human diseases. A hypothetical model is proposed in which long normal RNA hairpins formed by the repeats may also be involved in pathogenesis.

Alleles↗

PubMedDate not supplied

[Clinical picture of patients with Huntington's disease in relation to the number of trinucleotide CAG repeats in IT-15 gene].

Huntington's disease (HD) is a neurological condition of progressive course that results from abnormally increased number of CAG repeats within IT-15 gene, coding for huntington. The main symptoms consist of choraetic movements, dementia, and characteropathy. The aim of the present study was to search for possible correlation between the age of the onset of HD, time from the onset, clinical status of the patients, and CAG repeats number. Ten patients were studied altogether. Modified UHDRS (MUHDRS) was applied for the estimation of patients' clinical status. The number of CAG repeats in examination of the IT-15 gene was determined by polymerase chain reaction (PCR) and separation of radioisotope labelled PCR product against DNA size marker in polyacrylamide gel. A negative significant correlation was found between the CAG repeats number and the disease onset age (r = -0.67; p < 0.05) and MUHDRS score (r = 0.75; p < 0.05), as well. Negative significant correlation between time from the onset and MUHDRS score (r = -0.95; p < 0.05) and negative correlation between summarised: time from the onset and CAG number on the one site and MUHDRS on the other (p = -0.91) were found, as well. Our findings indicate an interdependence between CAG repeats number within the IT-15 gene, the course of the disease and the clinical status of HD patients.

Adolescent↗