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Biochimica Et Biophysica Acta. Gene... Mar 2019
Review
Topics: Adenine; Animals; Humans; Protein Biosynthesis; RNA Processing, Post-Transcriptional; RNA, Messenger
PubMed: 30342175
DOI: 10.1016/j.bbagrm.2018.10.006 -
Cold Spring Harbor Protocols May 2021This protocol provides details for nuclease S1 mapping of mRNA using a uniformly labeled, single-stranded DNA probe. DNA-RNA hybrids are generated, which are...
This protocol provides details for nuclease S1 mapping of mRNA using a uniformly labeled, single-stranded DNA probe. DNA-RNA hybrids are generated, which are subsequently digested with nuclease S1. The digestion products are separated using gel electrophoresis and analyzed by radiography.
Topics: DNA; Fungal Proteins; Nuclease Protection Assays; Nucleic Acid Hybridization; RNA; RNA, Messenger; Single-Strand Specific DNA and RNA Endonucleases
PubMed: 33941666
DOI: 10.1101/pdb.prot101824 -
Biochemical Society Transactions Apr 2017Messenger RNA (mRNA) translation and mRNA degradation are important determinants of protein output, and they are interconnected. Previously, it was thought that... (Review)
Review
Messenger RNA (mRNA) translation and mRNA degradation are important determinants of protein output, and they are interconnected. Previously, it was thought that translation of an mRNA, as a rule, prevents its degradation. mRNA surveillance mechanisms, which degrade mRNAs as a consequence of their translation, were considered to be exceptions to this rule. Recently, however, it has become clear that many mRNAs are degraded co-translationally, and it has emerged that codon choice, by influencing the rate of ribosome elongation, affects the rate of mRNA decay. In this review, we discuss the links between translation and mRNA stability, with an emphasis on emerging data suggesting that codon optimality may regulate mRNA degradation.
Topics: Codon; Eukaryota; Protein Biosynthesis; RNA Stability; RNA, Messenger; Ribosomes
PubMed: 28408474
DOI: 10.1042/BST20160243 -
Communications Biology Aug 2021Lipid Nanoparticles (LNPs) are used to deliver siRNA and COVID-19 mRNA vaccines. The main factor known to determine their delivery efficiency is the pKa of the LNP...
Lipid Nanoparticles (LNPs) are used to deliver siRNA and COVID-19 mRNA vaccines. The main factor known to determine their delivery efficiency is the pKa of the LNP containing an ionizable lipid. Herein, we report a method that can predict the LNP pKa from the structure of the ionizable lipid. We used theoretical, NMR, fluorescent-dye binding, and electrophoretic mobility methods to comprehensively measure protonation of both the ionizable lipid and the formulated LNP. The pKa of the ionizable lipid was 2-3 units higher than the pKa of the LNP primarily due to proton solvation energy differences between the LNP and aqueous medium. We exploited these results to explain a wide range of delivery efficiencies in vitro and in vivo for intramuscular (IM) and intravascular (IV) administration of different ionizable lipids at escalating ionizable lipid-to-mRNA ratios in the LNP. In addition, we determined that more negatively charged LNPs exhibit higher off-target systemic expression of mRNA in the liver following IM administration. This undesirable systemic off-target expression of mRNA-LNP vaccines could be minimized through appropriate design of the ionizable lipid and LNP.
Topics: Administration, Intravenous; Animals; Drug Compounding; Gene Expression; Humans; Hydrogen-Ion Concentration; Injections, Intramuscular; Ions; Lipids; Mice; Molecular Structure; Nanoparticles; RNA, Messenger; Spectrum Analysis; Tissue Distribution; Transfection
PubMed: 34381159
DOI: 10.1038/s42003-021-02441-2 -
Molecular Systems Biology 2006The past few years have brought about a fundamental change in our understanding and definition of the RNA world and its role in the functional and regulatory...
The past few years have brought about a fundamental change in our understanding and definition of the RNA world and its role in the functional and regulatory architecture of the cell. The discovery of small RNAs that regulate many aspects of differentiation and development have joined the already known non-coding RNAs that are involved in chromosome dosage compensation, imprinting, and other functions to become key players in regulating the flow of genetic information. It is also evident that there are tens or even hundreds of thousands of other non-coding RNAs that are transcribed from the mammalian genome, as well as many other yet-to-be-discovered small regulatory RNAs. In the recent symposium RNA: Networks & Imaging held in Heidelberg, the dual roles of RNA as a messenger and a regulator in the flow of genetic information were discussed and new molecular genetic and imaging methods to study RNA presented.
Topics: Animals; Humans; Molecular Biology; RNA; RNA Interference; RNA, Messenger; Transcription, Genetic
PubMed: 16924265
DOI: 10.1038/msb4100086 -
Chemical Communications (Cambridge,... Jun 2023We identify and characterize an RNA G-quadruplex (rG4) structure motif in the human microRNA 638 (hsa-miR-638). We investigate the formation and role of this rG4 and in...
We identify and characterize an RNA G-quadruplex (rG4) structure motif in the human microRNA 638 (hsa-miR-638). We investigate the formation and role of this rG4 and in cells, and reveal that it inhibits the miR-638 and MEF2C messenger RNA interaction and controls gene expression at the translational level.
Topics: Humans; RNA, Messenger; MicroRNAs; RNA; G-Quadruplexes; Gene Expression
PubMed: 37309572
DOI: 10.1039/d3cc01549a -
Scientific American Apr 1989
Review
Topics: Animals; Gene Expression Regulation; Protein Biosynthesis; Proteins; RNA, Messenger; Ribonucleases
PubMed: 2648565
DOI: 10.1038/scientificamerican0489-48 -
Epigenomics Dec 2021
Topics: Humans; RNA; RNA Processing, Post-Transcriptional; RNA, Messenger
PubMed: 34676794
DOI: 10.2217/epi-2021-0355 -
Chemical Communications (Cambridge,... Oct 2018A supramolecular catiomer with a metal-organic framework (MOF) motif was developed to manufacture messenger RNA (mRNA) assemblies. In contrast to the linear catiomer,...
A supramolecular catiomer with a metal-organic framework (MOF) motif was developed to manufacture messenger RNA (mRNA) assemblies. In contrast to the linear catiomer, the dendritic MOF catiomer appeared to markedly improve the colloidal stability of the mRNA assemblies, particularly affording substantial protection to the mRNA payloads from enzymatic degradation, eventually conducing to appreciable mRNA transfection activities at the targeted cells.
Topics: Cations; Cell Line, Tumor; Drug Carriers; Humans; Macromolecular Substances; Metal-Organic Frameworks; Particle Size; RNA, Messenger; Transfection
PubMed: 30234872
DOI: 10.1039/c8cc07047d -
Methods in Molecular Biology (Clifton,... 1998
Topics: Buffers; Chromatography, Affinity; Diethyl Pyrocarbonate; Eukaryotic Cells; Humans; Indicators and Reagents; Molecular Biology; Oligodeoxyribonucleotides; RNA, Messenger; Spectrophotometry, Ultraviolet
PubMed: 9664454
DOI: 10.1385/0-89603-494-1:61