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SRSF1 IS AN RNA-BINDING PROTEIN THAT FUNCTIONS AS A TRANSCRIPTIONAL ACTIVATOR
Title
SRSF1 IS AN RNA-BINDING PROTEIN THAT FUNCTIONS AS A TRANSCRIPTIONAL ACTIVATOR.
Creator
Paz, Sean, Caputi, Massimo, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description
Serine/Arginine splicing factor 1 (SRSF1) is an RNA-binding protein (RBP) with multiple functions in RNA biogenesis. SRSF1 plays a prominent role in oncogenesis, immune function, and response to several physiological stimuli. To date, the role of SRSF1 as a regulator of mRNA splicing has been largely considered the main mechanism driving its biological functions and its role in disease. We have now characterized SRSF1’s role in Human Immunodeficiency Virus Type I (HIV-1) transcription. SRSF1...
Show moreSerine/Arginine splicing factor 1 (SRSF1) is an RNA-binding protein (RBP) with multiple functions in RNA biogenesis. SRSF1 plays a prominent role in oncogenesis, immune function, and response to several physiological stimuli. To date, the role of SRSF1 as a regulator of mRNA splicing has been largely considered the main mechanism driving its biological functions and its role in disease. We have now characterized SRSF1’s role in Human Immunodeficiency Virus Type I (HIV-1) transcription. SRSF1 interacts with the 7SK small nuclear ribonucleoprotein (snRNP) to mobilize and activate the positive transcription-elongation factor (P-TEFb), which is then positioned on the HIV-1 promoter to increase the processivity of RNA polymerase II (RNAPolII) and promote the release of the negative regulators of transcription DSIF/NELF. Next, we defined the role of SRSF1 in the transcription of cellular genes utilizing an RNA sequencing (RNASeq) time course approach was used to detect changes in the transcriptome in response to SRSF1 overexpression. RNASeq data analysis revealed a subset of genes that were upregulated in response to SRSF1 overexpression. Nuclear run-on and qPCR assays experimentally validated 28 of these genes.
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Date Issued
2022
PURL
http://purl.flvc.org/fau/fd/FA00014112
Subject Headings
Transcription Factors, Serine-Arginine Splicing Factors, RNA-Binding Proteins, HIV
Format
Document (PDF)
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)