Impact of TNRC6 isoforms on gene expression and splicing
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA682956 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13207026.fastq.gz | Fastqsanger.gz | |||
| SRR13207027.fastq.gz | Fastqsanger.gz | |||
| SRR13207028.fastq.gz | Fastqsanger.gz | |||
| SRR13207029.fastq.gz | Fastqsanger.gz | |||
| SRR13207030.fastq.gz | Fastqsanger.gz |
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Project description:Through the RNA interference (RNAi) pathway, small RNAs can influence translation, splicing, transcriptional activation, and transcriptional repression. RNAi is carried out by the targeting Argonaute (Ago) effector protein and the facilitating TNRC6 (also known as GW182) scaffolding protein. Here, we use a suite of gene knockout cell lines and high-throughput sequencing to gather definitive answers about the TNRC6 paralogs, their roles in the cell, and their relation to Ago knockout cell lines. Each subsequent TNRC6 paralog knockout caused more gene changes and few genes overlapped between the single TNRC6 paralog knockouts. In addition, TNRC6 knockout and Ago knockout cell lines’ gene expression profiles are highly correlated with one another, indicating the important regulatory functions these proteins share. Overall we found that in spite of less than 40% sequence identity, TNRC6 paralogs are functionally redundant and can replace one another for core RNAi functions.
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Project description:TNRC6 is a scaffolding protein that bridges interactions between small RNAs, argonaute (AGO) protein, and effector proteins to control gene expression. There are three paralogs in mammalian cells, TNRC6A, TNRC6B, and TNRC6C These paralogs have ∼40% amino acid sequence identity and the extent of their unique or redundant functions is unclear. Here, we use knockout cell lines, enhanced crosslinking immunoprecipitation (eCLIP), and high-throughput RNA sequencing (RNA-seq) to explore the roles of TNRC6 paralogs in RNA-mediated control of gene expression. We find that the paralogs are largely functionally redundant and changes in levels of gene expression are well-correlated with those observed in AGO knockout cell lines. Splicing changes observed in AGO knockout cell lines are also observed in TNRC6 knockout cells. These data further define the roles of the TNRC6 isoforms as part of the RNA interference (RNAi) machinery.
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Project description:We aimed to study impact of CDC-like kinase (CLK) inhibitor CaNDY on OAS1 splicing manipulation. Our data indicates CaNDY treatment induces switching of OAS1 splice isoforms to provide an increased resistance to SARS-CoV-2 infection.
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Project description:To identify aberrant splicing isoforms and potential neoantigens, we performed full-length cDNA sequencing of lung adenocarcinoma cell lines using a long-read sequencer MinION. We constructed a comprehensive catalog of aberrant splicing isoforms and detected isoform-specific peptides using proteome analysis.
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Project description:The aim of this study was to obtain a landscape of alternative splicing (AS) in human hepatocellular carcinoma (HCC). We applied hybrid sequencing by integrating Pacbio long-read and Illumina short-read RNA sequencing data from 8 patient-derived HCC cell lines, and used an immortalized hepatocyte cell line as reference. This study revealed features of annotated and novel splice variants in HCC cells, including transcript length, AS type and protein changes. We also identified novel isoforms and tumor specific isoforms, which may represent potential biomarkers and targets for therapeutic development.
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