Emral Devany - Academia.edu (original) (raw)
Papers by Emral Devany
American Biology Teacher, Aug 31, 2023
Journal on excellence in college teaching, 2020
11th European Congress of Endocrinology, Apr 1, 2009
The physiological and pathophysiological significance of hGH isoforms remains to be fully elucida... more The physiological and pathophysiological significance of hGH isoforms remains to be fully elucidated. In order to study the two most abundant hGH isoforms 20 and 22 kDa hGH, we have generated monoclonal antibodies (mAbs) against 20 and 22 kDa hGH. The mAbs against ...
Cell discovery, Jun 14, 2016
Mucosal Immunology, Nov 1, 2009
Methods in molecular biology, 2014
Messenger RNA deadenylation is a process that allows rapid regulation of gene expression in respo... more Messenger RNA deadenylation is a process that allows rapid regulation of gene expression in response to different cellular conditions. The change of the mRNA poly(A) tail length by the activation of deadenylation might regulate gene expression by affecting mRNA stability, mRNA transport, or translation initiation. Activation of deadenylation processes are highly regulated and associated with different cellular conditions such as cancer, development, mRNA surveillance, DNA damage response, and cell differentiation. In the last few years, new technologies for studying deadenylation have been developed. Here we overview concepts related to deadenylation and its regulation in eukaryotic cells. We also describe some of the most commonly used protocols to study deadenylation in eukaryotic cells.
Proceedings of the National Academy of Sciences of the United States of America, Feb 11, 2013
Teaching English in the Two-Year College
Although the p53 network has been intensively studied, genetic analyses long hinted at the existe... more Although the p53 network has been intensively studied, genetic analyses long hinted at the existence of components that remained elusive. This dissertation focuses on the study of the regulation of mRNA 3\u27 processing during DNA damage response (DDR) by the p53 pathway and the regulation of p53 expression by the mRNA 3\u27 processing machinery. The results in this dissertation revealed new roles of tumor suppressor p53 in mRNA 3\u27 processing. In Chapter II, I showed that p53 inhibits the cleavage step of polyadenylation reaction and that cells with different levels of p53 expression have different mRNA processing profiles. As part of the same response to DNA damage, my results indicate that p53 also activates PARN-dependent deadenylation in the nucleus (Chapter III). In Chapter IV, I demonstrated that p53 mRNA is one of the biological targets of nuclear PARN under non-stress conditions. Extending these studies, in Chapter V, I established that both AU-rich element (ARE) and miR-...
PARN deadenylase is involved in miRNA-dependent
Journal on excellence in college teaching, 2020
RNA biology, Jan 15, 2017
Nucleolin (NCL) is an abundant stress-responsive, RNA-binding phosphoprotein that controls gene e... more Nucleolin (NCL) is an abundant stress-responsive, RNA-binding phosphoprotein that controls gene expression by regulating either mRNA stability and/or translation. NCL binds to the AU-rich element (ARE) in the 3'UTR of target mRNAs, mediates miRNA functions in the nearby target sequences, and regulates mRNA deadenylation. However, the mechanism by which NCL phosphorylation affects these functions and the identity of the deadenylase involved, remain largely unexplored. Earlier we demonstrated that NCL phosphorylation is vital for cell cycle progression and proliferation, whereas phosphorylation-deficient NCL at six consensus CK2 sites confers dominant-negative effect on proliferation by increasing p53 expression, possibly mimicking cellular DNA damage conditions. In this study, we show that NCL phosphorylation at those CK2 consensus sites in the N-terminus is necessary to induce deadenylation upon oncogenic stimuli and UV stress. NCL-WT, but not hypophosphorylated NCL-6/S*A, activ...
Cell discovery, 2016
The DNA damage response involves coordinated control of gene expression and DNA repair. Using dee... more The DNA damage response involves coordinated control of gene expression and DNA repair. Using deep sequencing, we found widespread changes of alternative cleavage and polyadenylation site usage on ultraviolet-treatment in mammalian cells. Alternative cleavage and polyadenylation regulation in the 3' untranslated region is substantial, leading to both shortening and lengthening of 3' untranslated regions of genes. Interestingly, a strong activation of intronic alternative cleavage and polyadenylation sites is detected, resulting in widespread expression of truncated transcripts. Intronic alternative cleavage and polyadenylation events are biased to the 5' end of genes and affect gene groups with important functions in DNA damage response and cancer. Moreover, intronic alternative cleavage and polyadenylation site activation during DNA damage response correlates with a decrease in U1 snRNA levels, and is reversible by U1 snRNA overexpression. Importantly, U1 snRNA overexpr...
Cancer Research, 2013
The phosphoprotein nucleolin integrates several critical cellular processes, such as cell growth,... more The phosphoprotein nucleolin integrates several critical cellular processes, such as cell growth, proliferation, cell cycle arrest, apoptosis as well as DDR. Elevated levels of nucleolin are found in highly proliferative cells including a variety of tumors. Nucleolin is highly phosphorylated at the N-terminus by two major kinases: interphase casein kinase 2 (CK2) and mitotic cyclin-dependent kinase (Cdk). Earlier we have demonstrated that the N-terminus of nucleolin associates with Hdm2 to stabilize p53 protein and causes p53-mediated apoptosis. Additionally, nucleolin via its RNA-binding properties has been demonstrated to regulate the stability of several mRNAs and enhance translation. Besides, nucleolin post-translational modifications are linked to its role as an RNA-binding stress-responsive protein. Based on these studies, we hypothesize a role for nucleolin phosphorylation in regulating mRNA stability of different target genes during DDR. To test this we have engineered a nov...
Methods in Molecular Biology, 2014
Messenger RNA deadenylation is a process that allows rapid regulation of gene expression in respo... more Messenger RNA deadenylation is a process that allows rapid regulation of gene expression in response to different cellular conditions. The change of the mRNA poly(A) tail length by the activation of deadenylation might regulate gene expression by affecting mRNA stability, mRNA transport, or translation initiation. Activation of deadenylation processes are highly regulated and associated with different cellular conditions such as cancer, development, mRNA surveillance, DNA damage response, and cell differentiation. In the last few years, new technologies for studying deadenylation have been developed. Here we overview concepts related to deadenylation and its regulation in eukaryotic cells. We also describe some of the most commonly used protocols to study deadenylation in eukaryotic cells.
Proceedings of the National Academy of Sciences, 2013
Although the p53 network has been intensively studied, genetic analyses long hinted at the existe... more Although the p53 network has been intensively studied, genetic analyses long hinted at the existence of components that remained elusive. Recent studies have shown regulation of p53 at the mRNA level mediated via both the 5′ and the 3′ untranslated regions and affecting the stability and translation efficiency of the p53 mRNA. Here, we provide evidence of a feedback loop between p53 and the poly(A)-specific ribonuclease (PARN), in which PARN deadenylase keeps p53 levels low in nonstress conditions by destabilizing p53 mRNA, and the UV-induced increase in p53 activates PARN deadenylase, regulating gene expression during DNA damage response in a transactivation-independent manner. This model is innovative because it provides insights into p53 function and the mechanisms behind the regulation of mRNA 3′ end processing in different cellular conditions.
Oncogene, Jan 7, 2011
The mechanisms involved in the p53-dependent control of gene expression following DNA damage have... more The mechanisms involved in the p53-dependent control of gene expression following DNA damage have not been completely elucidated. Here, we show that the p53 C terminus associates with factors that are required for the ultraviolet (UV)-induced inhibition of the mRNA 3' cleavage step of the polyadenylation reaction, such as the tumor suppressor BARD1 and the 3' processing factor cleavage-stimulation factor 1 (CstF1). We found that p53 can coexist in complexes with CstF and BARD1 in extracts of UV-treated cells, suggesting a role for p53 in mRNA 3' cleavage following DNA damage. Consistent with this, we found that p53 inhibits 3' cleavage in vitro and that there is a reverse correlation between the levels of p53 expression and the levels of mRNA 3' cleavage under different cellular conditions. Supporting these results, a tumor-associated mutation in p53 not only decreases the interaction with BARD1 and CstF, but also decreases the UV-induced inhibition of 3...
American Biology Teacher, Aug 31, 2023
Journal on excellence in college teaching, 2020
11th European Congress of Endocrinology, Apr 1, 2009
The physiological and pathophysiological significance of hGH isoforms remains to be fully elucida... more The physiological and pathophysiological significance of hGH isoforms remains to be fully elucidated. In order to study the two most abundant hGH isoforms 20 and 22 kDa hGH, we have generated monoclonal antibodies (mAbs) against 20 and 22 kDa hGH. The mAbs against ...
Cell discovery, Jun 14, 2016
Mucosal Immunology, Nov 1, 2009
Methods in molecular biology, 2014
Messenger RNA deadenylation is a process that allows rapid regulation of gene expression in respo... more Messenger RNA deadenylation is a process that allows rapid regulation of gene expression in response to different cellular conditions. The change of the mRNA poly(A) tail length by the activation of deadenylation might regulate gene expression by affecting mRNA stability, mRNA transport, or translation initiation. Activation of deadenylation processes are highly regulated and associated with different cellular conditions such as cancer, development, mRNA surveillance, DNA damage response, and cell differentiation. In the last few years, new technologies for studying deadenylation have been developed. Here we overview concepts related to deadenylation and its regulation in eukaryotic cells. We also describe some of the most commonly used protocols to study deadenylation in eukaryotic cells.
Proceedings of the National Academy of Sciences of the United States of America, Feb 11, 2013
Teaching English in the Two-Year College
Although the p53 network has been intensively studied, genetic analyses long hinted at the existe... more Although the p53 network has been intensively studied, genetic analyses long hinted at the existence of components that remained elusive. This dissertation focuses on the study of the regulation of mRNA 3\u27 processing during DNA damage response (DDR) by the p53 pathway and the regulation of p53 expression by the mRNA 3\u27 processing machinery. The results in this dissertation revealed new roles of tumor suppressor p53 in mRNA 3\u27 processing. In Chapter II, I showed that p53 inhibits the cleavage step of polyadenylation reaction and that cells with different levels of p53 expression have different mRNA processing profiles. As part of the same response to DNA damage, my results indicate that p53 also activates PARN-dependent deadenylation in the nucleus (Chapter III). In Chapter IV, I demonstrated that p53 mRNA is one of the biological targets of nuclear PARN under non-stress conditions. Extending these studies, in Chapter V, I established that both AU-rich element (ARE) and miR-...
PARN deadenylase is involved in miRNA-dependent
Journal on excellence in college teaching, 2020
RNA biology, Jan 15, 2017
Nucleolin (NCL) is an abundant stress-responsive, RNA-binding phosphoprotein that controls gene e... more Nucleolin (NCL) is an abundant stress-responsive, RNA-binding phosphoprotein that controls gene expression by regulating either mRNA stability and/or translation. NCL binds to the AU-rich element (ARE) in the 3'UTR of target mRNAs, mediates miRNA functions in the nearby target sequences, and regulates mRNA deadenylation. However, the mechanism by which NCL phosphorylation affects these functions and the identity of the deadenylase involved, remain largely unexplored. Earlier we demonstrated that NCL phosphorylation is vital for cell cycle progression and proliferation, whereas phosphorylation-deficient NCL at six consensus CK2 sites confers dominant-negative effect on proliferation by increasing p53 expression, possibly mimicking cellular DNA damage conditions. In this study, we show that NCL phosphorylation at those CK2 consensus sites in the N-terminus is necessary to induce deadenylation upon oncogenic stimuli and UV stress. NCL-WT, but not hypophosphorylated NCL-6/S*A, activ...
Cell discovery, 2016
The DNA damage response involves coordinated control of gene expression and DNA repair. Using dee... more The DNA damage response involves coordinated control of gene expression and DNA repair. Using deep sequencing, we found widespread changes of alternative cleavage and polyadenylation site usage on ultraviolet-treatment in mammalian cells. Alternative cleavage and polyadenylation regulation in the 3' untranslated region is substantial, leading to both shortening and lengthening of 3' untranslated regions of genes. Interestingly, a strong activation of intronic alternative cleavage and polyadenylation sites is detected, resulting in widespread expression of truncated transcripts. Intronic alternative cleavage and polyadenylation events are biased to the 5' end of genes and affect gene groups with important functions in DNA damage response and cancer. Moreover, intronic alternative cleavage and polyadenylation site activation during DNA damage response correlates with a decrease in U1 snRNA levels, and is reversible by U1 snRNA overexpression. Importantly, U1 snRNA overexpr...
Cancer Research, 2013
The phosphoprotein nucleolin integrates several critical cellular processes, such as cell growth,... more The phosphoprotein nucleolin integrates several critical cellular processes, such as cell growth, proliferation, cell cycle arrest, apoptosis as well as DDR. Elevated levels of nucleolin are found in highly proliferative cells including a variety of tumors. Nucleolin is highly phosphorylated at the N-terminus by two major kinases: interphase casein kinase 2 (CK2) and mitotic cyclin-dependent kinase (Cdk). Earlier we have demonstrated that the N-terminus of nucleolin associates with Hdm2 to stabilize p53 protein and causes p53-mediated apoptosis. Additionally, nucleolin via its RNA-binding properties has been demonstrated to regulate the stability of several mRNAs and enhance translation. Besides, nucleolin post-translational modifications are linked to its role as an RNA-binding stress-responsive protein. Based on these studies, we hypothesize a role for nucleolin phosphorylation in regulating mRNA stability of different target genes during DDR. To test this we have engineered a nov...
Methods in Molecular Biology, 2014
Messenger RNA deadenylation is a process that allows rapid regulation of gene expression in respo... more Messenger RNA deadenylation is a process that allows rapid regulation of gene expression in response to different cellular conditions. The change of the mRNA poly(A) tail length by the activation of deadenylation might regulate gene expression by affecting mRNA stability, mRNA transport, or translation initiation. Activation of deadenylation processes are highly regulated and associated with different cellular conditions such as cancer, development, mRNA surveillance, DNA damage response, and cell differentiation. In the last few years, new technologies for studying deadenylation have been developed. Here we overview concepts related to deadenylation and its regulation in eukaryotic cells. We also describe some of the most commonly used protocols to study deadenylation in eukaryotic cells.
Proceedings of the National Academy of Sciences, 2013
Although the p53 network has been intensively studied, genetic analyses long hinted at the existe... more Although the p53 network has been intensively studied, genetic analyses long hinted at the existence of components that remained elusive. Recent studies have shown regulation of p53 at the mRNA level mediated via both the 5′ and the 3′ untranslated regions and affecting the stability and translation efficiency of the p53 mRNA. Here, we provide evidence of a feedback loop between p53 and the poly(A)-specific ribonuclease (PARN), in which PARN deadenylase keeps p53 levels low in nonstress conditions by destabilizing p53 mRNA, and the UV-induced increase in p53 activates PARN deadenylase, regulating gene expression during DNA damage response in a transactivation-independent manner. This model is innovative because it provides insights into p53 function and the mechanisms behind the regulation of mRNA 3′ end processing in different cellular conditions.
Oncogene, Jan 7, 2011
The mechanisms involved in the p53-dependent control of gene expression following DNA damage have... more The mechanisms involved in the p53-dependent control of gene expression following DNA damage have not been completely elucidated. Here, we show that the p53 C terminus associates with factors that are required for the ultraviolet (UV)-induced inhibition of the mRNA 3' cleavage step of the polyadenylation reaction, such as the tumor suppressor BARD1 and the 3' processing factor cleavage-stimulation factor 1 (CstF1). We found that p53 can coexist in complexes with CstF and BARD1 in extracts of UV-treated cells, suggesting a role for p53 in mRNA 3' cleavage following DNA damage. Consistent with this, we found that p53 inhibits 3' cleavage in vitro and that there is a reverse correlation between the levels of p53 expression and the levels of mRNA 3' cleavage under different cellular conditions. Supporting these results, a tumor-associated mutation in p53 not only decreases the interaction with BARD1 and CstF, but also decreases the UV-induced inhibition of 3...