Embryos across metazoan lineages can enter reversible states of developmental pausing, or diapause, in response to adverse environmental conditions. The molecular mechanisms that underlie this remarkable dormant state remain largely unknown. Here we show that N-methyladenosine (mA) RNA methylation by Mettl3 is required for developmental pausing in mouse blastocysts and embryonic stem (ES) cells. Mettl3 enforces transcriptional dormancy through two interconnected mechanisms: (1) it promotes global mRNA destabilization and (2) it suppresses global nascent transcription by destabilizing the mRNA of the transcriptional amplifier and oncogene N-Myc, which we identify as a crucial anti-pausing factor. Knockdown of N-Myc rescues pausing in Mettl3 ES cells, and forced demethylation and stabilization of Mycn mRNA in paused wild-type ES cells largely recapitulates the transcriptional defects of Mettl3 ES cells. These findings uncover Mettl3 as a key orchestrator of the crosstalk between transcriptomic and epitranscriptomic regulation during developmental pausing, with implications for dormancy in adult stem cells and cancer.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619322 | PMC |
| http://dx.doi.org/10.1038/s41556-023-01212-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Prosodic Modifications to Challenging Communicative Environments in Preschoolers.
Lang Speech
January 2025
Department of Educational Psychology, Leadership, & Counseling, Texas Tech University, USA.
Adapting one's speaking style is particularly crucial as children start interacting with diverse conversational partners in various communication contexts. The study investigated the capacity of preschool children aged 3-5 years ( = 28) to modify their speaking styles in response to background noise, referred to as noise-adapted speech, and when talking to an interlocutor who pretended to have hearing loss, referred to as clear speech. We examined how two modified speaking styles differed across the age range.
View Article and Find Full Text PDFAs a NICU parent, I was always wondering how my daughter could sleep through all of the noise in the NICU what with her very early birth. I was already concerned about her developmental outcomes due to the birth itself, but the alarms and noise in the NICU gave me incredible pause. So when I found about DREAMIES, a product that helps muffle the noise not only in the NICU but during transport and during an MRI, I was amazed.
View Article and Find Full Text PDFA novel open-source cultivation system helps establish the first full cycle chemosynthetic symbiosis model system involving the giant ciliate .
Front Microbiol
December 2024
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, United States.
Symbiotic interactions drive species evolution, with nutritional symbioses playing vital roles across ecosystems. Chemosynthetic symbioses are globally distributed and ecologically significant, yet the lack of model systems has hindered research progress. The giant ciliate and its sulfur-oxidizing symbionts represent the only known chemosynthetic symbiosis with a short life span that has been transiently cultivated in the laboratory.
View Article and Find Full Text PDFClinical and cost-effectiveness of parenting intervention for mothers experiencing psychosocial stress: insights from the early closure of the Mellow Babies RCT.
Public Health Res (Southampt)
December 2024
Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK.
Background: Problems in children's early social and emotional development are likely to have major long-term consequences for the individual and society: maternal emotional well-being is associated with better outcomes. Interventions designed to improve both maternal mental health and the mother-child relationship are thus likely to benefit both maternal health and child development.
Objectives: To establish the clinical and cost-effectiveness of the Mellow Babies parenting intervention for women experiencing psychosocial stress and their 6- to 18-month-old babies.
Evaluative comparison of machine learning algorithms for stutter detection and classification.
MethodsX
December 2024
Department of Artificial Intelligence and Machine Learning, Symbiosis International University Symbiosis Institute of Technology, Pune, Maharashtra, India.
Stuttering is a neuro-developmental speech disorder that interrupts the flow of speech due to involuntary pauses and sound repetitions. It has profound psychological impacts that affect social interactions and professional advancements. Automatically detecting stuttering events in speech recordings could assist speech therapists or speech pathologists track the fluency of people who stutter (PWS).
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!