N-methyladenosine (mA) is the most prevalent modified nucleotide in mRNA, with around 25% of mRNAs containing at least one mA. Methylation of mRNA to form mA is required for diverse cellular and physiological processes. Although the presence of mA in an mRNA can affect its fate in different ways, it is unclear how mA directs this process and why the effects of mA can vary in different cellular contexts. Here we show that the cytosolic mA-binding proteins-YTHDF1, YTHDF2 and YTHDF3-undergo liquid-liquid phase separation in vitro and in cells. This phase separation is markedly enhanced by mRNAs that contain multiple, but not single, mA residues. Polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their low-complexity domains and thereby leading to phase separation. The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated compartments, such as P-bodies, stress granules or neuronal RNA granules. mA-mRNA is subject to compartment-specific regulation, including a reduction in the stability and translation of mRNA. These studies reveal that the number and distribution of mA sites in cellular mRNAs can regulate and influence the composition of the phase-separated transcriptome, and suggest that the cellular properties of mA-modified mRNAs are governed by liquid-liquid phase separation principles.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662915 | PMC |
| http://dx.doi.org/10.1038/s41586-019-1374-1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Tough Polyurethane Hydrogels with a Multiple Hydrogen-Bond Interlocked Bicontinuous Phase Structure Prepared by In Situ Water-Induced Microphase Separation.
Adv Mater
December 2024
Engineering Research Center of Energy Storage Materials and Devices Ministry of Education, School of Chemistry, Xi'an Jiaotong University, Xi'an, 710049, China.
Hydrogels with mechanical performances similar to load-bearing tissues are in demand for in vivo applications. In this work, inspired by the self-assembly behavior of amphiphilic polymers, polyurethane-based tough hydrogels with a multiple hydrogen-bond interlocked bicontinuous phase structure through in situ water-induced microphase separation strategy are developed, in which poly(ethylene glycol)-based polyurethane (PEG-PU, hydrophilic) and poly(ε-caprolactone)-based polyurethane (PCL-PU, hydrophobic) are blended to form dry films followed by water swelling. A multiple hydrogen bonding factor, imidazolidinyl urea, is introduced into the synthesis of the two polyurethanes, and the formation of multiple hydrogen bonds between PEG-PU and PCL-PU can promote homogeneous microphase separation for the construction of bicontinuous phase structures in the hydrogel network, by which the hydrogel features break strength of 12.
View Article and Find Full Text PDFBicontinuous Block Copolymer Microparticles through Hydrogen-Bonding-Mediated Dual Phase Separation between Polymer Segments and Fluorinated Additives.
ACS Nano
December 2024
Key Laboratory of Materials Chemistry for Energy Conversion and Storage of Ministry of Education (HUST), Hubei Key Laboratory of Materials Chemistry and Service Failure, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, China.
Bicontinuous microparticles have advanced transport, mechanical, and electrochemical properties and show promising applications in energy storage, catalysis, and other fields. However, it remains a great challenge to fabricate bicontinuous microparticles of block copolymers (BCPs) by controlling the microphase separation due to the extremely narrow region of a bicontinuous structure in the phase diagram. Here, we demonstrate a strategy to balance the phase separation of BCPs and fluorinated additives at different length scales in emulsion droplets, providing a large window to access bicontinuous microparticles.
View Article and Find Full Text PDFTrifluoroacetic Acid as a Molecular Probe for the Dense Phase in Liquid-Liquid Phase-Separating Peptide Systems.
Anal Chem
December 2024
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore.
Although trifluoroacetic acid (TFA) is not typically considered a Hofmeister reagent, it has been demonstrated to modulate biocoacervation. We show that TFA can be employed to probe specific interactions in coacervating bioinspired peptide phenylalanine (Phe) F-labeled at a single site, altering its liquid-liquid phase separation (LLPS) behavior. Solid-state nuclear magnetic resonance (NMR) spectroscopy revealed two dynamically distinct binding modes of TFA with Phe, resulting in a structured, dipolar-ordered complex and a more dynamic complex, highlighting the proximity between TFA and Phe.
View Article and Find Full Text PDFLC-ESI-MS/MS is a preferred method for detecting and identifying metabolites, including those that are unpredictable from the genome, especially in basal metazoans like Cnidaria, which diverged earlier than bilaterians and whose metabolism is poorly understood. However, the unexpected appearance of a "ghost peak" for dopamine, which exhibited the same m/z value and MS/MS product ion spectrum during an analysis of Nematostella vectensis, a model cnidarian, complicated its accurate identification. Understanding the mechanism by which "ghost peaks" appear is crucial to accurately identify the monoamine repertoire in early animals so as to avoid misassignments.
View Article and Find Full Text PDFThe Nuclear Condensates of ESE3/EHF Induce Cellular Senescence without the Associated Inflammatory Secretory Phenotype in Pancreatic Ductal Adenocarcinoma.
Cancer Lett
December 2024
Pancreas Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, PR China. Electronic address:
Senescent cells are in a stable state of cell cycle arrest, leading to a natural barrier to tumorigenesis. Senescent cells secrete a pool of molecules, including cytokines, chemokines, proteases, and growth factors, termed the senescence-associated secretory phenotype (SASP), paradoxically contributing to pro-tumorigenic processes. However, the mechanism for regulating senescence and SASP in tumor cells remains unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!