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The RNA Binding Protein SRSF1 modulates Immune and Cancer pathways by regulating MyD88 transcription
Title
The RNA Binding Protein SRSF1 modulates Immune and Cancer pathways by regulating MyD88 transcription.
Creator
Ritchie, Anastasia, Caputi, Massimo, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description
Serine/Arginine splicing factor 1 (SRSF1), a member of the Serine/Arginine rich (SR) RNA-binding proteins (RBPs) family, regulates mRNA biogenesis at multiple steps and is deregulated in cancer and autoimmune diseases. Preliminary studies show that members of the SR protein family play a role in cellular transcription. We investigated SRSF1’s role in cellular gene transcription utilizing time-course RNA-Seq and nuclear run-on assays, validating a subset of genes transcriptionally regulated...
Show moreSerine/Arginine splicing factor 1 (SRSF1), a member of the Serine/Arginine rich (SR) RNA-binding proteins (RBPs) family, regulates mRNA biogenesis at multiple steps and is deregulated in cancer and autoimmune diseases. Preliminary studies show that members of the SR protein family play a role in cellular transcription. We investigated SRSF1’s role in cellular gene transcription utilizing time-course RNA-Seq and nuclear run-on assays, validating a subset of genes transcriptionally regulated following SRSF1 overexpression. Pathway analysis showed that genes in the TNF/IL17 pathways were enriched in this dataset. Furthermore, we showed that MyD88, a strong activator of TNF transcription through transcription factors NF-κB and AP-1, is a primary target of SRSF1’s transcriptional activity. We propose that SRSF1 activates the transcription factors NF-κB and AP-1 through MyD88 pathway. SRSF1 overexpression regulates several genes that are deregulated in malignancies and immune disease, suggesting a role for SRSF1’s transcriptional activity in oncogenesis and immune response regulation.
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Date Issued
2020
PURL
http://purl.flvc.org/fau/fd/FA00013569
Subject Headings
RNA-Binding Proteins, Serine-Arginine Splicing Factors, Cancer, Autoimmune diseases, Transcription, Genetic, RNA, Messenger, Myeloid Differentiation Factor 88.
Format
Document (PDF)
Study of the Coupling Between Transcription and mRNA Processing Utilizing a Novel Bcl-x Mini-gene
Title
Study of the Coupling Between Transcription and mRNA Processing Utilizing a Novel Bcl-x Mini-gene.
Creator
Devanney, Sean C., Caputi, Massimo, Florida Atlantic University
Abstract/Description
The Bel family of genes are fundamental to the apoptotic mechanism. Bcl-x a member of this family, is alternatively spliced to create two main isoforms a long (Bcl-xL) and a short (Bcl-xS) variant. The long form exhibits anti-apoptotic activity, while the short form favors apoptosis. The proper balance of expression of these two isoforms is crucial for several developmental processes such as thymic selection and neural reshaping. A number of cancer types have been shown to over-express the...
Show moreThe Bel family of genes are fundamental to the apoptotic mechanism. Bcl-x a member of this family, is alternatively spliced to create two main isoforms a long (Bcl-xL) and a short (Bcl-xS) variant. The long form exhibits anti-apoptotic activity, while the short form favors apoptosis. The proper balance of expression of these two isoforms is crucial for several developmental processes such as thymic selection and neural reshaping. A number of cancer types have been shown to over-express the long form, thereby granting them some protection from apoptosis. To study the transcriptional and post-transcriptional mechanisms regulating gene expression, the Bcl-x gene has been utilized. A complex mini-gene construct has been create in order to monitor the effects that promoter sequences, 5'UTR and 3'UTR's have on mRNA splicing, RNA export, stability and translation. Abundant evidence exists indicating that RNA processing events such as transcription, splicing and export are coupled, yet the mechanisms and factors involved in regulating these processes are poorly understood. The mini-gene is identical to the endogenous gene with the exception of a deletion to the 50Kb intron and the addition of a tag to differentiate the mini-gene product from the endogenous mRNA and protein. This novel system allows for the study of transcriptional and post-transcriptional mechanisms regulating gene expression from RNA biogenesis on to the protein level.
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Date Issued
2007
PURL
http://purl.flvc.org/fau/fd/FA00000741
Subject Headings
Genetic transcription, Proteins--Synthesis, Messenger RNA, Gene expression, Oncogenes--Research
Format
Document (PDF)
Relationships between the global structure of genetic networks and mRNA levels measured by cDNA microarrays
Title
Relationships between the global structure of genetic networks and mRNA levels measured by cDNA microarrays.
Creator
Liebovitch, Larry S., Shehadeh, Lina A., Jirsa, Viktor K.
Date Issued
2006-05-16
PURL
http://purl.flvc.org/fau/165446
Subject Headings
DNA microarrays, DNA--genetics, Gene Expression Regulation, DNA- protein interactions, Genetic regulation, Messenger RNA--Analysis
Format
Document (PDF)