A5039308914- RNA Research and Splicing
- RNA modifications and cancer
- RNA regulation and disease
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Genetics, Bioinformatics, and Biomedical Research
- interferon and immune responses
University of California, Los Angeles
2019-2024
Terasaki Foundation
2020-2022
La Jolla Bioengineering Institute
2018-2020
Bioengineering Center
2018
In eukaryotes, nascent RNA transcripts undergo an intricate series of processing steps to achieve mRNA maturation. editing and alternative splicing are two major that can introduce significant modifications the final gene products. By tackling these processes in isolation, recent studies have enabled substantial progress understanding their global targets regulatory pathways. However, interplay between individual processing, essential aspect regulation, remains poorly understood. sequencing...
Adenosine-to-inosine (A-to-I) editing, mediated by the ADAR enzymes, diversifies transcriptome altering RNA sequences. Recent studies reported global changes in editing disease and development. Such widespread variations necessitate an improved understanding of regulatory mechanisms editing. Here, we study roles >200 RNA-binding proteins (RBPs) mediating two human cell lines. Using RNA-sequencing protein-RNA binding data, identify a number RBPs as key regulators A-to-I These RBPs, such...
Abstract Although long-read RNA-seq is increasingly applied to characterize full-length transcripts it can also enable detection of nucleotide variants, such as genetic mutations or RNA editing sites, which significantly under-explored. Here, we present an in-depth study detect and analyze sites in RNA-seq. Our new method, L-GIREMI, effectively handles sequencing errors read biases. Applied PacBio data, L-GIREMI affords a high accuracy identification. Additionally, our analysis uncovered...
Abstract Allele-specific protein-RNA binding is an essential aspect that may reveal functional genetic variants (GVs) mediating post-transcriptional regulation. Recently, genome-wide detection of in vivo RNA-binding proteins greatly facilitated by the enhanced crosslinking and immunoprecipitation (eCLIP) method. We developed a new computational approach, called BEAPR, to identify allele-specific (ASB) events eCLIP-Seq data. BEAPR takes into account crosslinking-induced sequence propensity...
RNA editing generates modifications to the sequences, thereby increasing protein diversity and shaping various layers of gene regulation. Recent studies have revealed global shifts in levels across many cancer types, as well a few specific mechanisms implicating individual sites tumorigenesis or metastasis. However, most tumor-associated sites, predominantly noncoding regions, unknown functional relevance.Here, we carry out integrative analysis profiles between epithelial mesenchymal tumors,...
Single-cell RNA sequencing (scRNA-seq) data contain rich information at the gene, transcript, and nucleotide levels. Most analyses of scRNA-seq have focused on gene expression profiles, it remains challenging to extract variants isoform-specific information. Here, we present scAllele, an integrative approach that detects single-nucleotide variants, insertions, deletions, their allelic linkage with splicing patterns in scRNA-seq. We demonstrate scAllele achieves better performance identifying...
RNA splicing plays a critical role in post-transcriptional gene regulation. Exponential expansion of intron length poses challenge for accurate splicing. Little is known about how cells prevent inadvertent and often deleterious expression intronic elements due to cryptic In this study, we identify hnRNPM as an essential binding protein that suppresses through deep introns, preserving transcriptome integrity. Long interspersed nuclear (LINEs) harbor large amounts pseudo splice sites introns....
Abstract Using third-generation sequencers, long-read RNA-seq is increasingly applied in transcriptomic studies given its major advantage characterizing full-length transcripts. A number of methods have been developed to analyze this new type data for transcript isoforms and their abundance. Another application, which significantly under-explored, identify single nucleotide variants (SNVs) the RNA. Identification SNVs, such as genetic mutations or RNA editing sites, fundamental many...
Genetic regulation of alternative splicing constitutes an important link between genetic variation and disease. Nonetheless, RNA is regulated by both
Abstract Allele-specific protein-RNA binding is an essential aspect that may reveal functional genetic variants influencing RNA processing and gene expression phenotypes. Recently, genome-wide detection of in vivo sites proteins (RBPs) greatly facilitated by the enhanced UV crosslinking immunoprecipitation (eCLIP) protocol. Hundreds eCLIP-Seq data sets were generated from HepG2 K562 cells during ENCODE3 phase. These afford a valuable opportunity to examine allele-specific (ASB) RBPs. To this...
Abstract Recent studies revealed global shifts in RNA editing, the modification of sequences, across many cancers. Besides a few sites implicated tumorigenesis or metastasis, most tumor-associated sites, predominantly noncoding regions, have unknown function. Here, we characterize editing profiles between epithelial (E) and mesenchymal (M) phenotypes seven cancer types, as epithelial-mesenchymal transition (EMT) is key paradigm for metastasis. We observe distinct patterns E M tumors EMT...
Abstract Single-cell RNA sequencing (scRNA-seq) data contain rich information at the gene, transcript, and nucleotide levels. Most analyses of scRNA-seq have focused on gene expression profiles, it remains challenging to extract variants isoform-specific information. Here, we present scAllele, an integrative approach that detects single variants, insertions, deletions, their allelic linkage with splicing patterns in scRNA-seq. We demonstrate scAllele achieves better performance identifying...