Search
Alternative splicing (AS) generates isoform diversity for cellular identity and homeostasis in multicellular life. Although AS variation has been observed among single cells, little is known about the biological or evolutionary significance of such variation. We developed Expedition, a computational …
Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5,954 tumors to reveal …
Dynamic regulation of RNA molecules is critical to the survival and development of cells. Messenger RNAs are transcribed in the nucleus as intron-containing pre-mRNAs and bound by RNA-binding proteins, which control their fate by regulating RNA stability, splicing, polyadenylation, translation, …
After an RNA is transcribed, it undergoes a variety of processing steps that can change the encoded protein sequence (through alternative splicing and RNA editing), regulate the stability of the RNA, and control subcellular localization, timing, and rate of translation. …
Host and virus interactions occurring at the post-transcriptional level are critical for infection but remain poorly understood. Here, we performed comprehensive transcriptome-wide analyses revealing that human cytomegalovirus (HCMV) infection results in widespread alternative splicing (AS), shortening of 3' untranslated regions …
HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role …
Embryonic stem cells (ESC) have the potential to generate all the cell lineages that form the body. However, the molecular mechanisms underlying ESC differentiation and especially the role of alternative splicing in this process remain poorly understood. Here, we show …
The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs …
Alternative splicing (AS) defects that adversely affect gene expression and function have been identified in diabetic hearts; however, the mechanisms responsible are largely unknown. Here, we show that the RNA-binding protein RBFOX2 contributes to transcriptome changes under diabetic conditions. RBFOX2 …
Endogenous retroviruses and retrotransposons contribute functional genetic variation in animal genomes. In mice, Intracisternal A Particles (IAPs) are a frequent source of both new mutations and polymorphism across laboratory strains. Intronic IAPs can induce alternative RNA processing choices, including alternative …
The RNA-binding protein FUS/TLS, mutation in which is causative of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS), is demonstrated to directly bind to the U1-snRNP and SMN complexes. ALS-causative mutations in FUS/TLS are shown to abnormally enhance their …
The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe …
Alternative splicing (AS) enables programmed diversity of gene expression across tissues and development. We show here that binding in distal intronic regions (>500 nucleotides (nt) from any exon) by Rbfox splicing factors important in development is extensive and is an …
Diabetic cardiomyopathy is one of the complications of diabetes that eventually leads to heart failure and death. Aberrant activation of PKC signaling contributes to diabetic cardiomyopathy by mechanisms that are poorly understood. Previous reports indicate that PKC is implicated in …
SR proteins are well-characterized RNA binding proteins that promote exon inclusion by binding to exonic splicing enhancers (ESEs). However, it has been unclear whether regulatory rules deduced on model genes apply generally to activities of SR proteins in the cell. …
Transactivating response region DNA binding protein (TDP-43) is the major protein component of ubiquitinated inclusions found in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions. Two ALS-causing mutants (TDP-43(Q331K) and TDP-43(M337V)), but not wild-type human TDP-43, …
FUS/TLS (fused in sarcoma/translocated in liposarcoma) and TDP-43 are integrally involved in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We found that FUS/TLS binds to RNAs from >5,500 genes in mouse and human brain, primarily through a GUGGU-binding motif. We …
LIN28 is a conserved RNA-binding protein implicated in pluripotency, reprogramming, and oncogenesis. It was previously shown to act primarily by blocking let-7 microRNA (miRNA) biogenesis, but here we elucidate distinct roles of LIN28 regulation via its direct messenger RNA (mRNA) …
Understanding how RNA binding proteins control the splicing code is fundamental to human biology and disease. Here, we present a comprehensive study to elucidate how heterogeneous nuclear ribonucleoparticle (hnRNP) proteins, among the most abundant RNA binding proteins, coordinate to regulate …
Transcriptome analysis by deep sequencing, more commonly known as RNA-seq is, becoming the method of choice for gene discovery and quantitative splicing detection. We published a double-random priming RNA-seq approach capable of generating strand-specific information [Li et al., Proc Natl …
We used cross-linking and immunoprecipitation coupled with high-throughput sequencing to identify binding sites in 6,304 genes as the brain RNA targets for TDP-43, an RNA binding protein that, when mutated, causes amyotrophic lateral sclerosis. Massively parallel sequencing and splicing-sensitive junction …
This chapter provides a review of recent advances in understanding the importance of alternative pre-messenger RNA splicing in stem cell biology. The majority of transcribed pre-mRNAs undergo RNA splicing where introns are excised and exons are juxtaposed to form mature …
The elucidation of a code for regulated splicing has been a long-standing goal in understanding the control of post-transcriptional gene expression events that are crucial for cell survival, differentiation and development. We decoded functional RNA elements in vivo by constructing …
High-throughput sequencing has rapidly gained popularity for transcriptome analysis in mammalian cells because of its ability to generate digital and quantitative information on annotated genes and to detect transcripts and mRNA isoforms. Here, we described a double-random priming method for …
Elucidating the molecular changes that arise during neural differentiation and fate specification is crucial for building accurate in vitro models of neurodegenerative diseases using human embryonic stem cells (hESCs). Here we review the importance of hESCs and derived progenitors in …
Comprehensive RNA-binding protein analyses using enhanced CLIP (ENCORE) [dataset2]
Comprehensive RNA-binding protein analyses using enhanced CLIP (ENCORE) [dataset1]
Single-cell and isoform-specific translational profiling of the mouse brain with long-read sequencing [scRNA-Seq, longread]
Single-cell and isoform-specific translational profiling of the mouse brain [scRNA-seq]
PUF60-Mediated Splicing Is a Key Driver of Triple Negative Breast Cancer [CRISPR]
PUF60-Mediated Splicing Is a Key Driver of Triple Negative Breast Cancer [eCLIP]
PUF60-Mediated Splicing Is a Key Driver of Triple Negative Breast Cancer [RNA-seq]
RNA-targeting Cas9 corrects molecular and physiological features in pre-clinical model of myotonic dystrophy type 1
RNA sequencing of bone marrow CD34+ hematopoietic stem and progenitor cells from patients with myelodysplastic syndrome and healthy controls
Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant myelodysplastic syndrome
Loss of nuclear TDP-43 in ALS causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurons
Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology
Loss of canonical splicing factor SRSF1 in hepatocytes results in acute liver injury and regeneration
Splicing Factor SRSF1 Deficiency in the Liver Triggers NASH-like Pathology via R-Loop Induced DNA Damage and Cell Death
In vivo CRISPR screening unveils RNA binding protein dependencies for leukemic stem cells and identifies ELAVL1 as a potential therapeutic target [eCLIPseq]
In vivo CRISPR screening unveils RNA binding protein dependencies for leukemic stem cells and identifies ELAVL1 as a potential therapeutic target [RNA-seq]
Exonuclease assisted mapping of protein-RNA interactions (ePRINT)
Exonuclease assisted mapping of protein-RNA interactions (ePRINT)
An in situ method for identification of transcriptome-wide protein-RNA interactions in cells [in_situ_STAMP]
An in situ method for identification of transcriptome-wide protein-RNA interactions in cells [eCLIP-seq ]
An in situ method for identification of transcriptome-wide protein-RNA interactions in cells [isSTAMP]
Aging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [RNA-seq]
Aging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [eCLIP-seq]
Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress. (2025)
Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress. (2025)
Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress. (2025)
Integrative CRISPR Screening and RNA Analyses Discover an Essential Role for PUF60 Interactions with 3' Splice Sites in Cancer Progression. (2025)
Integrative CRISPR Screening and RNA Analyses Discover an Essential Role for PUF60 Interactions with 3' Splice Sites in Cancer Progression. (2025)
Integrative CRISPR Screening and RNA Analyses Discover an Essential Role for PUF60 Interactions with 3' Splice Sites in Cancer Progression. (2025)
Integrative CRISPR Screening and RNA Analyses Discover an Essential Role for PUF60 Interactions with 3' Splice Sites in Cancer Progression. (2025)
Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion. (2024)
Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion. (2024)
Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion. (2024)
Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes. (2024)
Splicing factor SRSF1 deficiency in the liver triggers NASH-like pathology and cell death. (2023)
Splicing factor SRSF1 deficiency in the liver triggers NASH-like pathology and cell death. (2023)
Integrative RNA-omics Discovers GNAS Alternative Splicing as a Phenotypic Driver of Splicing Factor-Mutant Neoplasms. (2022)
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing. (2022)
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors. (2022)
Integrative RNA-omics Discovers GNAS Alternative Splicing as a Phenotypic Driver of Splicing Factor-Mutant Neoplasms. (2022)
The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors. (2022)
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors. (2022)
The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors. (2022)