- RNA Research and Splicing
- Japanese History and Culture
- Political theory and Gramsci
- Viral Infections and Immunology Research
- RNA and protein synthesis mechanisms
- Political Economy and Marxism
- Chinese history and philosophy
- Elite Sociology and Global Capitalism
- RNA modifications and cancer
- RNA regulation and disease
- Irish and British Studies
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Anarchism and Radical Politics
- Viral Infectious Diseases and Gene Expression in Insects
- Wnt/β-catenin signaling in development and cancer
- Italian Fascism and Post-war Society
- Plant Virus Research Studies
- Fungal and yeast genetics research
- Balkans: History, Politics, Society
- Developmental Biology and Gene Regulation
- Fibroblast Growth Factor Research
- Korean Peninsula Historical and Political Studies
- Immune Cell Function and Interaction
- Socioeconomic Development in Asia
University of the West of Scotland
2015-2021
Medical College of Wisconsin
2009-2020
Faculty of Media
2008-2019
University of Hawaiʻi at Mānoa
2008-2018
Children’s Institute
2018
University of Leeds
2009-2011
University of Essex
2008-2009
Dún Laoghaire Institute of Art, Design and Technology
2005
Johns Hopkins University
1991-1993
Johns Hopkins Medicine
1992
The human immunodeficiency virus type 1 (HIV-1) genome contains 20 exons that are alternatively spliced from 16 splice sites to generate more than 40 different mRNAs, including incompletely and unspliced mRNAs. In contrast avian retroviral RNA, which has acis-acting element ingagthat negatively regulates splicing (NRS), HIV-1 RNA did not have any NRS sequences in thegagorpolgenes detectable by a inhibition assay. However, this assay demonstrated the first 5′ site competed with cellular site,...
Mice exposed to radiation-attenuated cercariae of Schistosoma mansoni are highly resistant challenge infection, and sera from these mice can confer partial resistance when transferred naive recipients. These recognize Ag present in schistosomular adult worms, among them an 200 kDa. A cDNA encoding a 62-kDa portion this was cloned; the deduced amino acid sequence clone shares homology with myosins other species. To assess immunoprophylactic potential, we carried out vaccination trials using...
Retroviruses splice only a fraction of their primary RNA transcripts to subgenomic mRNA. The unspliced is transported the cytoplasm, where it serves as genomic well mRNA for gag and pol genes. Deletion sequences from Rous sarcoma virus gene, which part intron mRNAs, was previously observed result in an increase ratio spliced RNA. These sequences, we termed negative regulator splicing (NRS), can be moved heterologous gene resulting accumulation nucleus. We have used such constructs, assayed...
A cis-acting negative regulator of splicing (NRS) within the gag gene RSV is involved in control relative levels spliced and unspliced viral mRNAs. Insertion NRS into intron an adenovirus pre-mRNA resulted inhibition vitro before first cleavage step. Analyses spliceosome assembly with this substrate showed that it formed large RNP complexes did not migrate like mature spliceosomes on native gels. Affinity selection NRS-containing pre-mRNAs association U11 U12 snRNPs, as well spliceosomal...
Heterogeneous nuclear ribonucleoprotein (hnRNP) H and F are members of a closely related subfamily hnRNP proteins that implicated in many aspects RNA processing. alternative splicing factors for numerous U2- U12-dependent introns. The have three binding domains two glycine-rich localize to both the nucleus cytoplasm, but little is known about which govern subcellular localization or activity. We show here central glycine-tyrosine-arginine-rich (GYR) domain responsible localization,...
cis-acting sequences of Rous sarcoma virus (RSV) RNA involved in control the incomplete splicing that is part retroviral life cycle have been studied. The 5' and two alternative 3' splice sites, as well negative regulator element intron, introduced into chimeric constructs, their responsive roles inhibition evaluated by transient transfection experiments. Although RSV site was used efficiently these assays, substrates containing either env or src were not spliced completely, resulting 40 to...
Neurospora crassa mutants resistant to 2-deoxyglucose have been isolated, and their mutations mapped four genetic loci. The the following characteristics: (i) they are sorbose as well 2-deoxyglucose; (ii) partially or completely constitutive for glucose transport system II, glucamylase, invertase, which usually repressed during growth on glucose; (iii) synthesize an invertase with abnormal thermostability immunological properties, suggesting altered posttranslational modification. All of...
Retroviral replication requires that a portion of the primary transcripts generated from proviral DNA be spliced to serve as mRNA for envelope protein and in Rous sarcoma virus src mRNA. However, substantial amount full-length RNA must maintained an unspliced form, serves both structural proteins virion-associated enzymatic genomic progeny virions. The extent viral splicing finely controlled, since only narrow range ratio is tolerated optimal replication. A number cis-acting sequences within...
Incomplete RNA splicing is a key feature of the retroviral life cycle. This in contrast to processing most cellular pre-mRNAs, which are usually spliced completion. In Rous sarcoma virus, control achieved part through cis-acting element termed negative regulator (NRS). The NRS functionally divided into two parts NRS5' and NRS3', bind number factors. U1 U11 small nuclear ribonucleoproteins interact with sequences whereas binds several proteins including members SR [corrected] family proteins....
The waved with open eyes (woe) locus is a spontaneous recessive mouse mutation that exhibits wavy fur, eyelids at birth, and enlarged heart esophagus. In this study, we confirmed the previously identified woe phenotypes additionally anterior eye segment defects, absence of meibomian glands, defects in semilunar cardiac valves. Positional cloning C794T substitution Adam17 gene ablates putative exonic splicing enhancer (ESE) sequence exon 7 resulting aberrant splicing. predominant transcript,...
Significance Oncogenic signaling by small GTPases enhances malignant phenotypes in both breast and lung cancer. The SmgGDS splice variant isoforms SmgGDS-607 SmgGDS-558 activate oncogenic promoting their prenylation. We report that a pathologic ratio of variants is expressed cancer cells associated with decreased survival patients. developed splice-switching oligonucleotide (SSO) to target this isoform ratio. This SSO suppresses prenylation GTPases, induces apoptotic cell death cells,...
The accumulation in infected cells of large amounts unspliced viral RNA for use as mRNA and genomic is a hallmark retrovirus replication. negative regulator splicing (NRS) longcis-acting element Rous sarcoma virus that contributes to through inhibition. One two critical sequences located the NRS 3′ region resembles minor class 5′ splice site required U11 small nuclear ribonucleoprotein (snRNP) binding NRS. second purine-rich half interacts with factor SF2/ASF. In this study we investigated...
ABSTRACT Retroviruses require both spliced and unspliced RNA for replication. Accumulation of Rous sarcoma virus is facilitated in part by a negative cis element the gag region, termed regulator splicing (NRS), which serves to repress viral but can also block heterologous introns. The NRS binds components machinery including SR proteins, U1 U2, small nuclear ribonucleoproteins (snRNPs) major pathway, U11 snRNP minor yet does not normally occur from NRS. A mutation that abolishes binding...
ABSTRACT Rous sarcoma virus (RSV) requires large amounts of unspliced RNA for replication. Splicing and polyadenylation are coupled in the cells they infect, which raises question how viral is efficiently polyadenylated absence splicing. Optimal RSV a far-upstream splicing control element, negative regulator (NRS), that binds SR proteins U1/U11 snRNPs functions as pseudo-5′ splice site interacts with sequesters 3′ sites. We investigated link between NRS-mediated inhibition efficient...
An RNA-processing element from Rous sarcoma virus, the negative regulator of splicing (NRS), represses to generate unspliced RNA that serves as mRNA and genomic for progeny virions also promotes polyadenylation RNA. Integral NRS function is binding U1 small nuclear ribonucleoprotein (snRNP), but its controlled by U11 snRNP binds an overlapping site. snRNP, counterpart U12-dependent introns, remarkably well requires G-rich elements just downstream consensus We present evidence heterogeneous...
We characterize a novel otoferlin mutation discovered in sibling pair diagnosed with auditory neuropathy spectrum disorder and investigate nerve function through their cochlear implants. Genetic sequencing revealed homozygous at the splice donor site of exon 28 (IVS28 + 1G>T) both siblings. Functional investigation showed that intronic sequence between exons 29 was retained mutated minigenes were expressed 293T cells. Auditory compound action potential recovery functions siblings...
ABSTRACT The negative regulator of splicing (NRS) from Rous sarcoma virus suppresses viral RNA and is one several cis elements that account for the accumulation large amounts unspliced use as gag-pol mRNA progeny virion genomic RNA. NRS can also inhibit heterologous introns in vivo vitro. Previous data showed factors SF2/ASF U1, U2, U11 small nuclear ribonucleoproteins (snRNPs) bind NRS, a correlation was established between binding activity, suggesting these are important function. These...