General Information of the m6A Target Gene (ID: M6ATAR00416)
Target Name Serine/arginine-rich splicing factor 3 (SRSF3)
Synonyms
Pre-mRNA-splicing factor SRP20; Splicing factor, arginine/serine-rich 3; SFRS3; SRP20
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Gene Name SRSF3
Chromosomal Location 6p21.31-p21.2
Family splicing factor SR family
Function
Splicing factor that specifically promotes exon-inclusion during alternative splicing. Interaction with YTHDC1, a RNA-binding protein that recognizes and binds N6-methyladenosine (m6A)-containing RNAs, promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing. Also functions as export adapter involved in mRNA nuclear export . Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway); enhances NXF1-NXT1 RNA-binding activity. Involved in nuclear export of m6A-containing mRNAs via interaction with YTHDC1: interaction with YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export. RNA-binding is semi-sequence specific .
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Gene ID 6428
Uniprot ID
SRSF3_HUMAN
HGNC ID
HGNC:10785
Ensembl Gene ID
ENSG00000112081
KEGG ID
hsa:6428
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
SRSF3 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
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Methyltransferase-like 3 (METTL3) [WRITER]
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line LNCaP cell line Homo sapiens
Treatment: shMETTL3 LNCaP cells
Control: shControl LNCaP cells
GSE147884
Regulation
logFC: -6.96E-01
p-value: 4.00E-41
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 3 (SRSF3), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression.
Target Regulation Up regulation
Responsed Disease Glioblastoma ICD-11: 2A00.00
Pathway Response RNA degradation hsa03018
Cell Process mRNA decay
In-vitro Model U251 (Fibroblasts or fibroblast like cells)
U-87MG ATCC Glioblastoma Homo sapiens CVCL_0022
In-vivo Model For subcutaneous tumor model, each mouse was injected subcutaneously in the right flank with 2 × 106 U87MG cells (METTL3-KD or control) in 100 uL PBS.
YTH domain-containing protein 1 (YTHDC1) [READER]
Representative RNA-seq result indicating the expression of this target gene regulated by YTHDC1
Cell Line ICM cell line Mus musculus
Treatment: YTHDC1 knockout ICM cells
Control: Wild type ICM cells
GSE157267
Regulation
logFC: -1.77E+00
p-value: 4.66E-05
More Results Click to View More RNA-seq Results
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 3 (SRSF3), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression.
Target Regulation Up regulation
Responsed Disease Glioblastoma ICD-11: 2A00.00
Pathway Response RNA degradation hsa03018
Cell Process mRNA decay
In-vitro Model U251 (Fibroblasts or fibroblast like cells)
U-87MG ATCC Glioblastoma Homo sapiens CVCL_0022
In-vivo Model For subcutaneous tumor model, each mouse was injected subcutaneously in the right flank with 2 × 106 U87MG cells (METTL3-KD or control) in 100 uL PBS.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary Kaposi's sarcoma-associated herpesvirus(KSHV) productive lytic replication plays a pivotal role in the initiation and progression of Kaposi's sarcoma tumors. m6A sites in RTA pre-mRNA crucial for splicing through interactions with YTHDC1, Serine/arginine-rich splicing factor 3 (SRSF3) and SRSF10. m6A in regulating RTA pre-mRNA splicing but also suggest that KSHV has evolved a mechanism to manipulate the host m6A machinery to its advantage in promoting lytic replication.
Target Regulation Up regulation
Responsed Disease Kaposi's sarcoma ICD-11: 2B57
Pathway Response Spliceosome hsa03040
In-vitro Model TIVE-KSHV (KSHV-infected telomerase-immortalized human umbilical vein endothelial cells (TIVE-KSHV cells))
iSLK-BAC16 cells (Kaposi's sarcoma cells carrying the recombinant KSHV bacterial artificial chromosome 16 (BAC16) (iSLK-BAC16 cells))
HUVEC-C Normal Homo sapiens CVCL_2959
Brain cancer [ICD-11: 2A00]
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 3 (SRSF3), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression.
Responsed Disease Glioblastoma [ICD-11: 2A00.00]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response RNA degradation hsa03018
Cell Process mRNA decay
In-vitro Model U251 (Fibroblasts or fibroblast like cells)
U-87MG ATCC Glioblastoma Homo sapiens CVCL_0022
In-vivo Model For subcutaneous tumor model, each mouse was injected subcutaneously in the right flank with 2 × 106 U87MG cells (METTL3-KD or control) in 100 uL PBS.
Experiment 2 Reporting the m6A-centered Disease Response [1]
Response Summary Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 3 (SRSF3), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression.
Responsed Disease Glioblastoma [ICD-11: 2A00.00]
Target Regulator YTH domain-containing protein 1 (YTHDC1) READER
Target Regulation Up regulation
Pathway Response RNA degradation hsa03018
Cell Process mRNA decay
In-vitro Model U251 (Fibroblasts or fibroblast like cells)
U-87MG ATCC Glioblastoma Homo sapiens CVCL_0022
In-vivo Model For subcutaneous tumor model, each mouse was injected subcutaneously in the right flank with 2 × 106 U87MG cells (METTL3-KD or control) in 100 uL PBS.
Kaposi's sarcoma [ICD-11: 2B57]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary Kaposi's sarcoma-associated herpesvirus(KSHV) productive lytic replication plays a pivotal role in the initiation and progression of Kaposi's sarcoma tumors. m6A sites in RTA pre-mRNA crucial for splicing through interactions with YTHDC1, Serine/arginine-rich splicing factor 3 (SRSF3) and SRSF10. m6A in regulating RTA pre-mRNA splicing but also suggest that KSHV has evolved a mechanism to manipulate the host m6A machinery to its advantage in promoting lytic replication.
Responsed Disease Kaposi's sarcoma [ICD-11: 2B57]
Target Regulator YTH domain-containing protein 1 (YTHDC1) READER
Target Regulation Up regulation
Pathway Response Spliceosome hsa03040
In-vitro Model TIVE-KSHV (KSHV-infected telomerase-immortalized human umbilical vein endothelial cells (TIVE-KSHV cells))
iSLK-BAC16 cells (Kaposi's sarcoma cells carrying the recombinant KSHV bacterial artificial chromosome 16 (BAC16) (iSLK-BAC16 cells))
HUVEC-C Normal Homo sapiens CVCL_2959
Pancreatic cancer [ICD-11: 2C10]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response []
Response Summary Serine/arginine-rich splicing factor 3 (SRSF3) promotes gemcitabine resistance by regulating ANRIL's splicing and ANRIL-208 (one of the ANRIL spliceosomes) can enhance DNA homologous recombination repair (HR) capacity by forming a complex with Ring1b and EZH2. Demonstrates that abnormal alternative splicing and m6A modification are closely related to chemotherapy resistance in pancreatic cancer.
Responsed Disease Pancreatic cancer [ICD-11: 2C10]
Responsed Drug Gemcitabine Approved
Pathway Response mRNA surveillance pathway hsa03015
Cell Process mRNA alternative splicing
In-vitro Model ()
()
In-vivo Model Gemcitabine-resistant Panc1 cells (Panc1-GR) were prepared as stable luciferase clones after transduction with CTRL or shSRSF3 or sh-ANRIL-L vector or SRSF3 or ANRIL-L. For the PDX models, pieces of fresh human pancreatic cancer tissues were transplanted subcutaneously into the axilla of 4-6 week-old NOD/SCID mice.
Gemcitabine [Approved]
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response []
Response Summary Serine/arginine-rich splicing factor 3 (SRSF3) promotes gemcitabine resistance by regulating ANRIL's splicing and ANRIL-208 (one of the ANRIL spliceosomes) can enhance DNA homologous recombination repair (HR) capacity by forming a complex with Ring1b and EZH2. Demonstrates that abnormal alternative splicing and m6A modification are closely related to chemotherapy resistance in pancreatic cancer.
Responsed Disease Pancreatic cancer ICD-11: 2C10
Pathway Response mRNA surveillance pathway hsa03015
Cell Process mRNA alternative splicing
In-vitro Model ()
()
In-vivo Model Gemcitabine-resistant Panc1 cells (Panc1-GR) were prepared as stable luciferase clones after transduction with CTRL or shSRSF3 or sh-ANRIL-L vector or SRSF3 or ANRIL-L. For the PDX models, pieces of fresh human pancreatic cancer tissues were transplanted subcutaneously into the axilla of 4-6 week-old NOD/SCID mice.
References
Ref 1 N(6)-Methyladenosine Modulates Nonsense-Mediated mRNA Decay in Human Glioblastoma. Cancer Res. 2019 Nov 15;79(22):5785-5798. doi: 10.1158/0008-5472.CAN-18-2868. Epub 2019 Sep 17.
Ref 2 Kaposi's Sarcoma-Associated Herpesvirus Utilizes and Manipulates RNA N(6)-Adenosine Methylation To Promote Lytic Replication. J Virol. 2017 Jul 27;91(16):e00466-17. doi: 10.1128/JVI.00466-17. Print 2017 Aug 15.