A5010172507- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- MicroRNA in disease regulation
- Neurogenetic and Muscular Disorders Research
- Gene expression and cancer classification
- Molecular Biology Techniques and Applications
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Single-cell and spatial transcriptomics
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- PI3K/AKT/mTOR signaling in cancer
- Genomics and Rare Diseases
- Gene Regulatory Network Analysis
- RNA Interference and Gene Delivery
- Cell death mechanisms and regulation
- Genetic factors in colorectal cancer
- Water resources management and optimization
- Groundwater and Isotope Geochemistry
- ATP Synthase and ATPases Research
- Cancer Genomics and Diagnostics
- RNA regulation and disease
- Enzyme Production and Characterization
University of Minnesota
2015-2024
University of Central Florida
2019-2020
University of Minnesota System
2019-2020
University of California, Davis
2019-2020
Masonic Cancer Center
2018
Chosun University
2017
Howard Hughes Medical Institute
2000-2012
University of Pennsylvania
2000-2012
California University of Pennsylvania
2006
Seoul National University
1996
The Survival of Motor Neurons (SMN) protein, the product spinal muscular atrophy–determining gene, is part a large macromolecular complex (SMN complex) that functions in assembly spliceosomal small nuclear ribonucleoproteins (snRNPs). Using cell extracts and purified components, we demonstrated SMN necessary sufficient to mediate ATP-dependent core seven Sm proteins on uridine-rich, ribonucleic acids (U snRNAs). In vitro experiments revealed strict requirements for ordered binding U snRNAs...
The survival of motor neurons (SMN) protein, the product neurodegenerative disease spinal muscular atrophy (SMA) gene, is localized both in cytoplasm and discrete nuclear bodies called gems. In compartments SMN part a large complex that contains several proteins including Gemin2 (formerly SIP1) DEAD box protein Gemin3. cytoplasm, associated with snRNP Sm core plays critical role spliceosomal assembly. nucleus, required for pre-mRNA splicing by serving regeneration spliceosomes. These...
Reduction of the survival motor neurons (SMN) protein levels causes neuron degenerative disease spinal muscular atrophy, severity which correlates with extent reduction in SMN. SMN, together Gemins 2 to 7, forms a complex that functions assembly small nuclear ribonucleoprotein particles (snRNPs). Complete depletion SMN from cell extracts abolishes snRNP assembly, formation heptameric Sm cores on snRNAs. However, what effect, if any, levels, as occurs atrophy patients, has capacity cells...
Mammalian target of rapamycin (mTOR) enhances translation from a subset messenger RNAs containing distinct 5′-untranslated region (UTR) sequence features. Here we identify 3′-UTR shortening mRNAs as an additional molecular signature mTOR activation and show that the specific mRNAs. Using genetic or chemical modulations activity in cells mouse tissues, cellular is crucial for shortening. Although long 3′-UTR-containing transcripts minimally contribute to translation, 3-′UTR-shortened...
Accurate disease phenotype prediction plays an important role in the treatment of heterogeneous diseases like cancer era precision medicine. With advent high throughput technologies, more comprehensive multi-omics data is now available that can effectively link genotype to phenotype. However, interactive relation datasets makes it particularly challenging incorporate different biological layers discover coherent signatures and predict phenotypic outcomes. In this study, we introduce...
To serve in its function as an assembly machine for spliceosomal small nuclear ribonucleoprotein particles (snRNPs), the survival of motor neurons (SMN) protein complex binds directly to Sm proteins and U snRNAs. A specific domain unique U1 snRNA, stem-loop 1 (SL1), is required SMN binding snRNP core assembly. Here, we show that each major snRNAs (U2, U4, U5), well minor splicing pathway U11 contains a which with remarkable affinity (low nanomolar concentration). The SMN-binding domains do...
MDC1 is critical component of the DNA damage response (DDR) machinery and orchestrates ensuring assembly DDR protein at sites, therefore loss results in genomic instability tumorigenicity. However, molecular mechanisms controlling expression are currently unknown. Here, we show that miR-22 inhibits translation via direct binding to its 3' untranslated region, leading impaired repair instability. We demonstrated activated Akt1 senescence hinder function by upregulating endogenous miR-22....
High-throughput spatial-transcriptomics RNA sequencing (sptRNA-seq) based on in-situ capturing technologies has recently been developed to spatially resolve transcriptome-wide mRNA expressions mapped the captured locations in a tissue sample. Due low capture efficiency by and complication of section preparation, sptRNA-seq data often only provides an incomplete profiling gene over spatial regions tissue. In this paper, we introduce graph-regularized tensor completion model for imputing...
Epithelial‐mesenchymal transition ( EMT ) is a critical response during cancer cell metastasis. In this study, we provide evidence that uncoordinated 51‐like kinase 2 ULK 2) regulates . Induction of autophagy by inhibition mammalian target rapamycin complex 1 mTORC 1) or disruption silencing raptor significantly enhanced , however, rictor had no effect. Knockdown expression induced autophagy, and migration but suppressed proliferation as well tumor growth in xenotransplantation model,...
Human APOBEC3H (A3H) is a single-stranded DNA cytosine deaminase that inhibits HIV-1. Seven haplotypes (I-VII) and four splice variants (SV154/182/183/200) with differing antiviral activities geographic distributions have been described, but the genetic mechanistic basis for variant expression function remains unclear. Using combined bioinformatic/experimental analysis, we find SV200 specific to haplotype II, which primarily found in sub-Saharan Africa. The underlying mechanism differential...
Spatial transcriptomics data play a crucial role in cancer research, providing nuanced understanding of the spatial organization gene expression within tumor tissues. Unraveling dynamics can unveil key insights into heterogeneity and aid identifying potential therapeutic targets. However, many large-scale studies, are limited, with bulk RNA-seq corresponding Whole Slide Image (WSI) being more common (e.g. TCGA project). To address this gap, there is critical need to develop methodologies...
The survival of motor neurons (SMN) complex is essential for the biogenesis spliceosomal small nuclear ribonucleoproteins (snRNPs) as it binds to and delivers Sm proteins assembly cores on abundant RNAs (snRNAs). Using conserved snRNAs encoded by lymphotropic Herpesvirus saimiri (HVS), we determined specific sequence structural features binding SMN core assembly. We show that minimal complex-binding domain in snRNAs, except U1, comprised an site (AUUUUUG) adjacent 3' stem-loop. adenosine...
3′-untranslated regions (UTRs) can vary through the use of alternative polyadenylation sites during pre-mRNA processing. Multiple publically available pipelines combining high profiling technologies and bioinformatics tools have been developed to catalog changes in 3′-UTR lengths. In our recent RNA-seq experiments using cells with hyper-activated mammalian target rapamycin (mTOR), we found that cellular mTOR activation leads transcriptome-wide (APA), resulting multiple pathways. Here, a...