scholarly journals RNA uridyl transferases TUT4/7 differentially regulate miRNA variants depending on the cancer cell-type

RNA ◽  
2021 ◽  
pp. rna.078976.121
Author(s):  
Ragini Medhi ◽  
Jonathan Price ◽  
Giulia Furlan ◽  
Beronia Gorges ◽  
Alexandra Sapetschnig ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cancer Therapies ◽  
Cell Type ◽  
Expression Levels ◽  
Mrna Targets ◽  
Specific Manner ◽  
Mirna Clusters ◽  
Cancer Cell Type ◽  
Cell Type Specific ◽  
And Migration

The human terminal uridyl transferases TUT4 and TUT7 (TUT4/7) catalyse the additions of uridines at the 3′ end of RNAs, including the precursors of the tumour suppressor miRNA let-7 upon recruitment by the oncoprotein LIN28A. As a consequence, let-7 family miRNAs are downregulated. Disruption of this TUT4/7 activity inhibits tumorigenesis. Hence, targeting TUT4/7 could be a potential anti-cancer therapy. In this study, we investigate TUT4/7-mediated RNA regulation in two cancer cell lines by establishing catalytic knockout models. Upon TUT4/7 mutation, we observe a significant reduction in miRNA uridylation, which results in defects in cancer cell properties such as cell proliferation and migration. With the loss of TUT4/7-mediated miRNA uridylation, the uridylated miRNA variants are replaced by adenylated isomiRs. Changes in miRNA modification profiles are accompanied by deregulation of expression levels in specific cases. Unlike let-7s, most miRNAs do not depend on LIN28A for TUT4/7-mediated regulation. Additionally, we identify TUT4/7-regulated cell-type-specific miRNA clusters and deregulation in their corresponding mRNA targets. Expression levels of miR-200c-3p and miR-141-3p are regulated by TUT4/7 in a cancer cell-type-specific manner. Subsequently, BCL2 which is a well-established target of miR-200c is upregulated. Therefore, TUT4/7 loss causes deregulation of miRNA-mRNA networks in a cell-type-specific manner. Understanding the underlying biology of such cell-type-specific deregulation will be an important aspect of targeting TUT4/7 for potential cancer therapies.

scholarly journals RNA uridyl transferases TUT4/7 differentially regulate miRNA variants depending on the cancer cell-type

2021 ◽  
Author(s):  
Ragini Medhi ◽  
Jonathan Price ◽  
Giulia Furlan ◽  
Beronia Gorges ◽  
Alexandra Sapetschnig ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cancer Cell ◽  
Cell Type ◽  
Expression Levels ◽  
Mrna Targets ◽  
Specific Manner ◽  
Mirna Clusters ◽  
Cancer Cell Type ◽  
Cell Type Specific ◽  
And Migration

The human terminal uridyl transferases TUT4 and TUT7 (TUT4/7) catalyse additions of uridines at the 3′ end of RNAs such as the precursors of the tumour suppressor miRNA let-7, upon recruitment by the oncoprotein LIN28A. Consequently, let-7 family miRNAs are downregulated. Disruption of this TUT4/7 activity inhibits tumorigenesis and hence targeting TUT4/7 can be a potential anti-cancer therapy. In this study, we investigate TUT4/7-mediated RNA regulation in two cancer cell lines by establishing catalytic knockout models. Upon TUT4/7 mutation, we observe a significant reduction in miRNA uridylation, which results in defects in cancer cell properties such as cell proliferation and migration. With the loss of TUT4/7-mediated miRNA uridylation, the uridylated miRNA variants are replaced by adenylated isomiRs. Changes in miRNA modification profiles are accompanied by deregulation of expression levels in specific cases. Unlike let-7s, most miRNAs do not depend on LIN28A for TUT4/7-mediated regulation. Additionally, we identify TUT4/7-regulated cell-type-specific miRNA clusters and deregulation in their corresponding mRNA targets. Expression levels of miR-200c-3p and miR-141-3p are regulated by TUT4/7 in a cancer cell type specific manner. Subsequently, BCL2 which is a well-established target of miR-200c is upregulated. Therefore, TUT4/7 loss triggers deregulation of miRNA-mRNA networks in a cell-type-specific manner. Understanding of the underlying biology of such cell-type-specific deregulation will be key when targeting TUT4/7 for cancer therapy.

scholarly journals Rel Induces Interferon Regulatory Factor 4 (IRF-4) Expression in Lymphocytes

2000 ◽  
Vol 191 (8) ◽  
pp. 1281-1292 ◽  
Author(s):  
Raelene J. Grumont ◽  
Steve Gerondakis
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Nuclear Factor Κb ◽  
Wild Type ◽  
Cell Type ◽  
Regulatory Factor ◽  
Specific Manner ◽  
A Cell ◽  
Cell Type Specific ◽  
Interferon Regulatory Factor 4

In lymphocytes, the Rel transcription factor is essential in establishing a pattern of gene expression that promotes cell proliferation, survival, and differentiation. Here we show that mitogen-induced expression of interferon (IFN) regulatory factor 4 (IRF-4), a lymphoid-specific member of the IFN family of transcription factors, is Rel dependent. Consistent with IRF-4 functioning as a repressor of IFN-induced gene expression, the absence of IRF-4 expression in c-rel−/− B cells coincided with a greater sensitivity of these cells to the antiproliferative activity of IFNs. In turn, enforced expression of an IRF-4 transgene restored IFN modulated c-rel−/− B cell proliferation to that of wild-type cells. This cross-regulation between two different signaling pathways represents a novel mechanism that Rel/nuclear factor κB can repress the transcription of IFN-regulated genes in a cell type–specific manner.

PLAG1 enhances the stemness profiles of acinar cells in normal human salivary glands in a cell type-specific manner

2020 ◽  
Vol 62 (1) ◽  
pp. 99-106 ◽  
Author(s):  
Yuriko Goto ◽  
Miho Ibi ◽  
Hirotaka Sato ◽  
Junichi Tanaka ◽  
Rika Yasuhara ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Acinar Cells ◽  
Cell Type ◽  
Specific Manner ◽  
A Cell ◽  
Normal Human ◽  
Cell Type Specific

scholarly journals Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type

2013 ◽  
Vol 12 (1) ◽  
pp. 11 ◽  
Author(s):  
Steven Rust ◽  
Sandrine Guillard ◽  
Kris Sachsenmeier ◽  
Carl Hay ◽  
Max Davidson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Type ◽  
Cancer Cell Type
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