Publications by authors named "Horvat F"
In RNA interference (RNAi), long double-stranded RNA is cleaved by the Dicer endonuclease into small interfering RNAs (siRNAs), which guide degradation of complementary RNAs. While RNAi mediates antiviral innate immunity in plants and many invertebrates, vertebrates have adopted a sequence-independent response and their Dicer produces siRNAs inefficiently because it is adapted to process small hairpin microRNA precursors in the gene-regulating microRNA pathway. Mammalian endogenous RNAi is thus a rudimentary pathway of unclear significance.
View Article and Find Full Text PDFIntroduction: Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related deaths worldwide with limited treatment options due to extensive radiation and chemotherapy resistance. Monotherapy with immune checkpoint blockade showed no survival benefit. A combination of immunomodulation and radiotherapy may offer new treatment strategies, as demonstrated for non-small cell lung cancer.
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- PIWI-interacting RNAs (piRNAs) are vital for maintaining genome integrity by silencing mobile genetic elements and are derived from long single-stranded precursors in various species.
- The study explores how piRNA clusters form and adapt to genomic threats, presenting a roadmap of piRNA clusters in seven species, highlighting shared traits and differences.
- Findings reveal transcriptional readthrough as a mechanism for piRNA production in mammals, especially in response to retroviral threats, and uncover dynamic piRNA clusters in human germ cells, enhancing understanding of piRNA biology across species.
Article Synopsis
- Canonical RNA interference (RNAi) is a process where small interfering RNAs (siRNAs) guide the breakdown of specific mRNAs, playing roles in gene regulation and defense mechanisms.
- In mammals, RNAi is typically limited due to Dicer producing microRNAs instead, but a specific variant (ΔHEL1) allows for RNAi in mouse oocytes, and mutations to this variant can lead to severe developmental issues.
- Research on Dicer mice shows they can exhibit increased siRNA levels without significant changes to their microRNA profiles, suggesting the possibility of using these mice to study the overall impacts and potential of RNAi in living organisms.
The translational oscillation in oocyte and early embryo development.
Nucleic Acids Res
December 2023
Article Synopsis
- Translation is essential for development, particularly during the silenced transcription phase of oocytes and early embryos.
- A genome-wide translatome analysis revealed that while global protein synthesis decreases during M-phases, the initiation and elongation of translation are activated, showing a dynamic shift in how specific mRNAs are translated.
- This study provides new insights into gene expression regulation during oocyte meiosis and the first two embryonic mitoses, marking a significant step towards understanding the molecular mechanisms of translation control in early development.
Article Synopsis
- Gene evolution is complex, with simpler genes like lncRNAs emerging de novo from non-genic sequences; however, protein-coding genes usually have ties to ancestral sequences.* -
- The study focuses on the evolution of the D6Ertd527e gene in rodents, which likely started as an lncRNA due to a retrotransposon insertion, eventually acquiring protein-coding abilities in some species.* -
- Although the D6Ertd527e gene shows limited function in lab mice, its evolutionary journey in rodents over the past ~40 million years illustrates key processes in gene formation and evolution.*
Article Synopsis
- Dicer endonucleases produce small RNAs for microRNA (miRNA) and RNA interference (RNAi) pathways, playing a crucial role in gene regulation.
- The DExD/H helicase domain of Dicer is vital for high-fidelity miRNA biogenesis, with its complete absence being lethal and its ATPase function being dispensable.
- Structural studies show that the DExD/H domain helps lock Dicer in a closed state for miRNA precursor selection, while mutations can lead to reduced selectivity and activation of the RNAi pathway.
miRNAs, ~22nt small RNAs associated with Argonaute (AGO) proteins, are important negative regulators of gene expression in mammalian cells. However, mammalian maternal miRNAs show negligible repressive activity and the miRNA pathway is dispensable for oocytes and maternal-to-zygotic transition. The stoichiometric hypothesis proposed that this is caused by dilution of maternal miRNAs during oocyte growth.
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- PIWI-interacting RNAs (piRNAs) play a crucial role in suppressing retrotransposons in germline cells, traditionally viewed as more essential for male fertility than female fertility in mammals like mice.
- Research on golden hamsters reveals that the piRNA pathway functions differently across sexes, with female hamsters becoming sterile due to the loss of the Mov10l1 RNA helicase, which is vital for piRNA biogenesis.
- Male hamsters also show significant reproductive issues, including problems with spermatogonia development and a rise in retrotransposon expression, highlighting that the piRNA pathway is crucial for fertility in both sexes and adapts to manage genomic threats.
Article Synopsis
- * As oocytes grow, miRNAs do not accumulate at the same rate as mRNAs, leading to a significant dilution effect and lower overall concentrations of miRNAs in fully grown oocytes.
- * This low abundance of miRNAs is seen across various mammalian species, indicating that miRNA inactivity is a common trait in oocytes rather than being specific to mice.
Introduction: The purpose of this paper is to present the development and design of an abdominal retractor which allows a single person to perform operations and the fixation of the operation instruments can be done with one hand. The additional devices make the operation more comfortable for surgeons.
Methods: Conventional measuring devices have been designed and applied for determining axial forces in a surgeon's forearm during operations.
Article Synopsis
- Tens of thousands of long non-coding RNA (lncRNA) genes exist, but only a few have established functions, especially in mouse oocytes where the role of lncRNAs like Sirena1 was previously unknown.
- Sirena1, the most expressed lncRNA in mouse oocytes, has evolved functions in RNA interference and is involved in regulating maternal mRNA through unique mechanisms, despite not affecting fertility directly.
- Knock-out studies show that while Sirena1 alters the maternal transcriptome and affects mitochondrial organization, it highlights the complex evolutionary role of lncRNAs which may not translate to significant laboratory impacts.
Article Synopsis
- The study investigates how the germline genome defends against retrotransposons, focusing on two small RNA pathways: the piRNA pathway and RNA interference (RNAi).
- Mice lacking the piRNA pathway are sterile males but fertile females, leading researchers to explore whether RNAi can compensate for this loss.
- The findings indicate that while the two pathways target different retrotransposon families, neither pathway alone is essential for ovarian development, and another mechanism likely prevents the mobilization of certain retrotransposons like LINE-1.
Main constraints for RNAi induced by expressed long dsRNA in mouse cells.
Life Sci Alliance
February 2019
Article Synopsis
- RNA interference (RNAi) involves the degradation of specific mRNA molecules guided by small interfering RNAs (siRNAs) created from long double-stranded RNA (dsRNA) by the enzyme Dicer.
- A study found that the main obstacle to effective RNAi in mammals is producing effective siRNAs, influenced by Dicer's activity and the structure of dsRNA.
- Unexpectedly, enhancing certain Dicer cofactors was shown to decrease RNAi efficiency, while the removal of the protein kinase R had little impact, indicating a complex interaction between RNAi and microRNA pathways in mammalian cells.
Article Synopsis
- The removal of the poly(A) tail from mRNA is a crucial process for regulating mRNA stability in eukaryotic cells, primarily carried out by the CCR4-NOT complex.
- In mammalian systems, the CCR4 component is essential for proper maternal function in mouse, hamster, and bovine oocytes, significantly affecting litter size and embryo development.
- Deletion of the CNOT6L gene in females leads to delays and issues in embryo development, indicating its vital role in the transition from oocyte to embryo, with distinct mRNA targeting by decapping and deadenylation processes.
Article Synopsis
- * A study found that LTRs from the ERVL retrotransposon class significantly influence gene expression during the oocyte-to-embryo transition in various species, including mice and humans, by activating transcription and altering gene sequences.
- * The research highlights that ERVL LTRs can recycle genetic material, such as pseudogenes into functional RNAs, and even contribute to the evolution of new genes, demonstrating their vast potential for reshaping genome expression and evolution.
Multiple and multipolar spindles are a generalized feature of microsporogenesis in a cultivar of Fuchsia. Only the first meiotic division occurs and gives rise to sporads with nine microspores. Variation in chromosomal complements of the microspores is illustrated by pollen polymorphism.
View Article and Find Full Text PDF[Cases of keartosis palmaris et plantaris of the Papillon-Lefèvre type].
Rad Med Fak Zagrebu
October 1971