Neural stem cells (NSCs) of the ventricular-subventricular zone (V-SVZ) generate numerous cell types. The uncoupling of mRNA transcript availability and translation occurs during the progression from stem to differentiated states. The mTORC1 kinase pathway acutely controls proteins that regulate mRNA translation. Inhibiting mTORC1 during differentiation is hypothesized to be critical for brain development since somatic mutations of mTORC1 regulators perturb brain architecture. Inactivating mutations of or genes cause tuberous sclerosis complex (TSC). TSC patients have growths near the striatum and ventricles. Here, it is demonstrated that V-SVZ NSC inactivation causes striatal hamartomas. removal altered translation factors, translatomes, and translational efficiency. Single nuclei RNA sequencing following loss of revealed changes in NSC activation states. The inability to decouple mRNA transcript availability and translation delayed differentiation leading to the retention of immature phenotypes in hamartomas. Taken together, is required for translational repression and differentiation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10724693 | PMC |
| http://dx.doi.org/10.1016/j.isci.2023.108442 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mir-615-5p inhibits cervical cancer progression by targeting TMIGD2.
Hereditas
January 2025
Obstetrics and Gynecology Medical Centre, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, No.105, Shaoshan Middle Road, Yuhua District, Changsha, 410007, Hunan, China.
Background: Cervical cancer (CC) is a prevalent gynecological malignancy, contributing to a substantial number of fatalities among women. MicroRNAs (miRNAs) have emerged as promising biomarkers with significant potential for the early detection and prognosis of CC.
Objective: This study aimed to explore the clinical significance and biological role of miR-615-5p in CC, with the goal of identifying novel biomarkers for this disease.
Transcriptome-wide dynamics of mA methylation in ISKNV and Siniperca chuatsi cells infected with ISKNV.
BMC Genomics
January 2025
State Key Laboratory of Biocontrol, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), China-ASEAN Belt and Road Joint Laboratory on Mariculture Technology, Guangdong Provincial Key Laboratory of Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Infectious spleen and kidney necrosis virus (ISKNV) is a highly virulent and rapidly transmissible fish virus that poses threats to the aquaculture of a wide variety of freshwater and marine fish. N6-methyladenosine (mA), recognized as a common epigenetic modification of RNA, plays an important regulatory role during viral infection. However, the impact of mA RNA methylation on the pathogenicity of ISKNV remains unexplored.
View Article and Find Full Text PDFCRISPR-Enabled Autonomous Transposable Element (CREATE) for RNA-based gene editing and delivery.
EMBO Rep
January 2025
Myeloid Therapeutics Inc., Cambridge, MA, 02139, USA.
To address a wide range of genetic diseases, genome editing tools that can achieve targeted delivery of large genes without causing double-strand breaks (DSBs) or requiring DNA templates are necessary. Here, we introduce CRISPR-Enabled Autonomous Transposable Element (CREATE), a genome editing system that combines the programmability and precision of CRISPR/Cas9 with the RNA-mediated gene insertion capabilities of the human LINE-1 (L1) element. CREATE employs a modified L1 mRNA to carry a payload gene, and a Cas9 nickase to facilitate targeted editing by L1-mediated reverse transcription and integration without relying on DSBs or DNA templates.
View Article and Find Full Text PDFSystematically developing a registry of splice-site creating variants utilizing massive publicly available transcriptome sequence data.
Nat Commun
January 2025
Division of Genome Analysis Platform Development, National Cancer Center Research Institute, Tokyo, Japan.
Genomic variants causing abnormal splicing play important roles in genetic disorders and cancer development. Among them, variants that cause the formation of novel splice-sites (splice-site creating variants, SSCVs) are particularly difficult to identify and often overlooked in genomic studies. Additionally, these SSCVs are frequently considered promising candidates for treatment with splice-switching antisense oligonucleotides (ASOs).
View Article and Find Full Text PDFDivergent roles of mA in orchestrating brown and white adipocyte transcriptomes and systemic metabolism.
Nat Commun
January 2025
Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center; Department of Medicine, BIDMC; Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.
N-methyladenosine (mA) is among the most abundant mRNA modifications, yet its cell-type-specific regulatory roles remain unclear. Here we show that mA methyltransferase-like 14 (METTL14) differentially regulates transcriptome in brown versus white adipose tissue (BAT and WAT), leading to divergent metabolic outcomes. In humans and mice with insulin resistance, METTL14 expression differs significantly from BAT and WAT in the context of its correlation with insulin sensitivity.
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!