Tight coordination of gene expression in the developing cerebellum is crucial for establishment of neuronal circuits governing motor and cognitive function. However, transcriptional changes alone do not explain all of the switches underlying neuronal differentiation. Here we unveiled a widespread and highly dynamic splicing program that affects synaptic genes in cerebellar neurons. The motifs enriched in modulated exons implicated the splicing factor Sam68 as a regulator of this program. Sam68 controls splicing of exons with weak branchpoints by directly binding near the 3' splice site and competing with U2AF recruitment. Ablation of Sam68 disrupts splicing regulation of synaptic genes associated with neurodevelopmental diseases and impairs synaptic connections and firing of Purkinje cells, resulting in motor coordination defects, ataxia, and abnormal social behavior. These findings uncover an unexpectedly dynamic splicing regulatory network that shapes the synapse in early life and establishes motor and cognitive circuitry in the developing cerebellum.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.celrep.2020.107703 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Decoding the mA epitranscriptomic landscape for biotechnological applications using a direct RNA sequencing approach.
Nat Commun
January 2025
National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, National Engineering Research Center for New Drug and Druggability (cultivation), Guangdong Province Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
Epitranscriptomic modifications, particularly N6-methyladenosine (mA), are crucial regulators of gene expression, influencing processes such as RNA stability, splicing, and translation. Traditional computational methods for detecting mA from Nanopore direct RNA sequencing (DRS) data are constrained by their reliance on experimentally validated labels, often resulting in the underestimation of modification sites. Here, we introduce pum6a, an innovative attention-based framework that integrates positive and unlabeled multi-instance learning (MIL) to address the challenges of incomplete labeling and missing read-level annotations.
View Article and Find Full Text PDFIdentification of a Novel HIV-1 Second-Generation Circulating Recombinant Form (CRF117_0107) in China.
AIDS Res Hum Retroviruses
January 2025
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.
Under the background of the main epidemic HIV strains (CRF01_AE and CRF07_BC) co-circulation in China, more HIV second-generation recombinant (SGR) strains with CRF01_AE and CRF07_BC as the backbone were also emerging. In this study, we characterize a novel HIV-1 second-generation circulating recombinant form (CRF117_0107) consisting of CRF01_AE and CRF07_BC fragments from three epidemiologically unrelated HIV-1-infected individuals. One near full-length genome (NFLG) sequence was amplified, sequenced, and spliced in two halves using RNA extracted from the plasma of a homosexual in Shenzhen, Guangdong Province.
View Article and Find Full Text PDFIdentification of G-quadruplex nucleic acid structures by high-throughput sequencing: A review.
Int J Biol Macromol
January 2025
School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China; Smart Medical Innovation Technology Center, Guangdong University of Technology, Guangzhou 510006, China. Electronic address:
G-quadruplexes (G4s) are non-canonical nucleic acid secondary structures formed by guanine-rich DNA or RNA sequences. These structures play pivotal roles in cellular processes, including DNA replication, transcription, RNA splicing, and protein translation. High-throughput sequencing has significantly advanced the study of G4s by enabling genome-wide mapping and detailed characterization.
View Article and Find Full Text PDFThe main sources of molecular organization in the cell. Atlas of self-organized and self-regulated dynamic biostructures.
Prog Biophys Mol Biol
January 2025
Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country, UPV/EHU, Leioa 48940, Spain.
One of the most important goals of contemporary biology is to understand the principles of the molecular order underlying the complex dynamic architecture of cells. Here, we present an overview of the main driving forces involved in the cellular molecular complexity and in the emergent functional dynamic structures, spanning from the most basic molecular organization levels to the complex emergent integrative systemic behaviors. First, we address the molecular information processing which is essential in many complex fundamental mechanisms such as the epigenetic memory, alternative splicing, regulation of transcriptional system, and the adequate self-regulatory adaptation to the extracellular environment.
View Article and Find Full Text PDFThe effect of LARP7 on gene expression during osteogenesis.
Mol Biol Rep
January 2025
Institute of Health Sciences, Department of Medical and Surgical Research, Hacettepe University, Ankara, Turkey.
Background: La-related protein 7 (LARP7) is a key regulator of RNA metabolism and is thought to play a role in various cellular processes. LARP7 gene autosomal recessive mutations are the cause of Alazami syndrome, which presents with skeletal abnormalities, intellectual disabilities, and facial dysmorphisms. This study aimed to determine the role of LARP7 in modulating gene expression dynamics during osteogenesis.
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!