Background: The modulation of mRNA levels across tissues and time is key for the establishment and operation of the developmental programs that transform the fertilized egg into a fully formed embryo. Although the developmental mechanisms leading to differential mRNA synthesis are heavily investigated, comparatively little attention is given to the processes of mRNA degradation and how these relate to the molecular programs controlling development.
Results: Here we combine timed collection of Drosophila embryos and unfertilized eggs with genome-wide microarray technology to determine the degradation patterns of all mRNAs present during early fruit fly development. Our work studies the kinetics of mRNA decay, the contributions of maternally and zygotically encoded factors to mRNA degradation, and the ways in which mRNA decay profiles relate to gene function, mRNA localization patterns, translation rates and protein turnover. We also detect cis-regulatory sequences enriched in transcripts with common degradation patterns and propose several proteins and microRNAs as developmental regulators of mRNA decay during early fruit fly development. Finally, we experimentally validate the effects of a subset of cis-regulatory sequences and trans-regulators in vivo.
Conclusions: Our work advances the current understanding of the processes controlling mRNA degradation during early Drosophila development, taking us one step closer to the understanding of mRNA decay processes in all animals. Our data also provide a valuable resource for further experimental and computational studies investigating the process of mRNA decay.
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http://dx.doi.org/10.1186/gb-2010-11-9-r93 | DOI Listing |
Int J Rheum Dis
January 2025
The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China.
Background: N6-methyladenosine (m6A) is one of the most conserved internal RNA modifications, which has been implicated in many biological processes, such as apoptosis and proliferation. Wilms tumor 1-associating protein (WTAP), as a key component of m6A methylation, is a nuclear protein that has been associated with the regulation of proliferation and apoptosis. Rheumatoid arthritis (RA), a systemic, infiltrating autoimmune disease, is characterized by synovial hyperplasia.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Physics, Novosibirsk State University, 2 Pirogov Str., Novosibirsk 630090, Russia.
Nowadays, nucleic acid derivatives capable of modulating gene expression at the RNA level have gained widespread recognition as promising therapeutic agents. A suitable degree of biological stability of oligonucleotide therapeutics is required for in vivo application; this can be most expeditiously achieved by the chemical modification of the internucleotidic phosphate group, which may also affect their cellular uptake, tissue distribution and pharmacokinetics. Our group has previously developed a strategy for the chemical modification of the phosphate group via the Staudinger reaction on a solid phase of the intermediate dinucleoside phosphite triester and a range of, preferably, electron deficient organic azides such as sulfonyl azides during automated solid-phase DNA synthesis according to the conventional β-cyanoethyl phosphoramidite scheme.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Institute of Physical Culture Sciences, University of Szczecin, 17C Narutowicza St., 70-240 Szczecin, Poland.
The transport of biological materials must protect samples from degradation and ensure courier safety. The main goal of this study was to evaluate the usefulness of a new type of container designed for the secured transport of biological material for storing samples for quantitative RNA analyses. This was achieved by analyzing changes in the expression of selected human leucocyte housekeeping genes (, , and ) using reverse transcription quantitative PCR (RT-qPCR) and digital PCR (RT-dPCR) techniques.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy.
Thrombin binding aptamer (TBA) is one of the best-known G-quadruplex (G4)-forming aptamers that efficiently binds to thrombin, resulting in anticoagulant effects. TBA also possesses promising antiproliferative properties. As with most therapeutic oligonucleotides, chemical modifications are critical for therapeutic applications, particularly to improve thermodynamic stability, resistance in biological environment, and target affinity.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Center of Clinical and Preclinical Research MEDIPARK, Pavol Jozef Šafarik University, 04011 Košice, Slovakia.
Breast cancer (BC) is one of the most prevalent forms of cancer globally, and has recently become the leading cause of cancer-related mortality in women. BC is a heterogeneous disease comprising various histopathological and molecular subtypes with differing levels of malignancy, and each patient has an individual prognosis. Etiology and pathogenesis are complex and involve a considerable number of genetic alterations and dozens of alterations in non-coding RNA expression.
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