A5103064199- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Parkinson's Disease Mechanisms and Treatments
- Nuclear Receptors and Signaling
- Amyotrophic Lateral Sclerosis Research
- RNA modifications and cancer
- Neurogenetic and Muscular Disorders Research
- Cryptographic Implementations and Security
- Genomics and Chromatin Dynamics
- Polyomavirus and related diseases
- Viral gastroenteritis research and epidemiology
- Chaos-based Image/Signal Encryption
- interferon and immune responses
- Nuclear Physics and Applications
- Clostridium difficile and Clostridium perfringens research
- Connexins and lens biology
- Epigenetics and DNA Methylation
- Alzheimer's disease research and treatments
- Neurological diseases and metabolism
- Radiation Detection and Scintillator Technologies
- Trace Elements in Health
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Enzyme Structure and Function
University College London
2013-2021
The Francis Crick Institute
2016-2018
National Hospital for Neurology and Neurosurgery
2016-2018
University of Modena and Reggio Emilia
2014
Institute of Genetics
2013
Background. An 18-month-old boy developed encephalopathy, for which extensive investigation failed to identify an etiology, 6 weeks after stem cell transplant. To exclude a potential infectious cause, we performed high-throughput RNA sequencing on brain biopsy.
Article15 May 2018Open Access Source DataTransparent process Mice with endogenous TDP-43 mutations exhibit gain of splicing function and characteristics amyotrophic lateral sclerosis Pietro Fratta Corresponding Author [email protected] orcid.org/0000-0002-8762-8188 UCL Institute Neurology, MRC Centre for Neuromuscular Disease, London, UK Search more papers by this author Prasanth Sivakumar Jack Humphrey Genetics Institute, Kitty Lo Thomas Ricketts Mammalian Unit, Harwell, Hugo Oliveira Jose...
Reliable exon recognition is key to the splicing of pre-mRNAs into mature mRNAs. TDP-43 an RNA-binding protein whose nuclear loss and cytoplasmic aggregation are a hallmark pathology in amyotrophic lateral sclerosis frontotemporal dementia (ALS/FTD). depletion causes aberrant inclusion cryptic exons range transcripts, but their extent, relevance disease pathogenesis whether they caused by other proteins implicated ALS/FTD unknown. We developed analysis pipeline discover quantify applied it...
Recursive splicing (RS) starts by defining an "RS-exon," which is then spliced to the preceding exon, thus creating a recursive 5′ splice site (RS-5ss). Previous studies focused on cryptic RS-exons, and now we find that exon junction complex (EJC) represses RS of hundreds annotated, mainly constitutive RS-exons. The core EJC factors, peripheral factors PNN RNPS1, maintain RS-exon inclusion repressing spliceosomal assembly RS-5ss. also blocks 5ss located near exon-exon junctions, microexons....
In this work, we show that Clostridium difficile phage ϕC2 transduces erm(B), which confers erythromycin resistance, from a donor to recipient strain at frequency of 10(-6) per PFU. The transductants were lysogenic for and contained the erm(B) gene in novel transposon, Tn6215. This element is 13,008 bp length contains 17 putative open reading frames (ORFs). It could also be transferred lower by filter mating.Clostridium major human pathogen causes diarrhea can persistent difficult resolve...
Alu elements are retrotransposons that frequently form new exons during primate evolution. Here, we assess the interplay of splicing repression by hnRNPC and nonsense-mediated mRNA decay (NMD) in quality control evolution Alu-exons. We identify 3100 Alu-exons show NMD more efficiently recognises transcripts with compared to other premature termination codons. However, some escape NMD, especially when an adjacent intron is retained, highlighting importance concerted NMD. evolutionary...
Association studies have identified several signals at the LRRK2 locus for Parkinson's disease (PD), Crohn's (CD) and leprosy. However, little is known about molecular mechanisms mediating these effects. To further characterize this locus, we fine-mapped risk association in 5,802 PD 5,556 controls using a dense genotyping array (ImmunoChip). Using samples from 134 post-mortem control adult human brains (UK Human Brain Expression Consortium), where up to ten brain regions were available per...
Stem cells have been found in most tissues/organs. These somatic stem produce replacements for lost and damaged cells, it is not completely understood how this regenerative capacity becomes diminished during aging. To study the possible involvement of epigenetic changes cell aging, we used murine hematopoiesis as a model system. Hematopoietic (HSCs) were enriched via Hoechst exclusion activity (SP-HSC) from young, medium-aged old mice subjected to comprehensive, global methylome (MeDIP-seq)...
Parkinson's disease (PD) is a common, adult-onset, neuro-degenerative disorder characterized by the degeneration of cardinal motor signs mainly due to loss dopaminergic neurons in substantia nigra. To date, researchers still have limited understanding key molecular events that provoke neurodegeneration this disease. Here, we present ParkDB, first queryable database dedicated gene expression PD. ParkDB contains complete set re-analyzed, curated and annotated microarray datasets. This resource...
Inactivating mutations in TSC1 and TSC2 cause tuberous sclerosis complex (TSC). The 2012 international consensus meeting on TSC diagnosis management agreed that the identification of a pathogenic or variant establishes TSC, even absence clinical signs. However, exons 25 31 are subject to alternative splicing. No variants causing clinically diagnosed have been reported these exons, raising possibility such would not TSC. We present truncating in-frame three individuals unlikely fulfil...
UCbase 2.0 (http://ucbase.unimore.it) is an update, extension and evolution of UCbase, a Web tool dedicated to the analysis ultraconserved sequences (UCRs). UCRs are 481 >200 bases sharing 100% identity among human, mouse rat genomes. They frequently located in genomic regions known be involved cancer or differentially expressed human leukemias carcinomas. platform-independent resource that includes updated version genome annotation (hg19), information linking disorders chromosomal...
Abstract Reliable exon recognition is key to the splicing of pre-mRNAs into mature mRNAs. TDP-43 an RNA-binding protein whose nuclear loss and cytoplasmic aggregation are a hallmark pathology in amyotrophic lateral sclerosis frontotemporal dementia (ALS/FTD). depletion causes aberrant inclusion cryptic exons range transcripts, but their extent, relevance disease pathogenesis whether they caused by other proteins implicated ALS/FTD unknown. We developed analysis pipeline discover quantify...
ABSTRACT It is challenging for RNA processing machineries to select exons within long intronic regions. We find that LINE repeat sequences (LINEs) contribute this selection by recruiting dozens of RNA-binding proteins (RBPs). This includes MATR3, which promotes binding PTBP1 multivalent sites in LINEs. Both RBPs repress splicing and 3’ end around LINEs, as demonstrated cultured human cells mouse brain. Notably, repressive preferentially bind evolutionarily young are confined deep These...
Abstract There is strong cumulative evidence for the involvement of miR-137 and its targets in aetiology schizophrenia. Here we test whether variants, especially rare miR137 binding sites are associated with schizophrenia an exome-sequenced sample 4225 cases 5834 controls. A weighted burden using 372 variants was significant at p=0.024. The size too small to implicate individual or genes but overall this finding provides further support hypothesis that disruption can increase risk...
Colonized travelers contribute to the pandemic spread of resistant intestinal bacteria.This study is first show that antimicrobial use during travel predisposes