File Download
Supplementary

postgraduate thesis: Characterization of arginine methylation of the RNA-binding protein Staufen in neurons

TitleCharacterization of arginine methylation of the RNA-binding protein Staufen in neurons
Authors
Issue Date2015
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Liao, A. A. [廖安]. (2015). Characterization of arginine methylation of the RNA-binding protein Staufen in neurons. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5634738
AbstractThe morphology and number of dendritic spines have been associated with learning and memory. Abnormality of spine morphogenesis has been found in patients suffering from cognitive disorders, such as autism. Major modulators of dendritic spines include proteins that regulate the actin cytoskeleton. Many of them are thought to be translated onsite where the dendritic spines are located, away from the nucleus of the neurons. This specificity is made possible by mRNA transcripts being transported along microtubules bound to RNA-binding proteins (RBP) forming a ribonucleoprotein complex. One of these RBPs is Staufen1, a double-stranded RNA-binding protein found ubiquitously throughout the body. Previous studies have shown that depletion of Staufen1 in neurons leads to impairment of dendritic spines and synaptic strength, but how the function of Staufen is regulated is not yet understood. Arginine methylation, catalyzed by a class of enzymes called protein arginine methyltransferases (PRMTs), is one of the key post-translational modifications that regulate protein function. The present study aims to investigate the possibility of arginine methylation as a regulatory mechanism for Staufen1. Here I found that two of the type I PRMTs, PRMT3 and PRMT8, are present in synaptoneurosome, a biochemical fraction of the brain which is enriched with synapses. Furthermore, Staufen1 was found to be arginine methylated in the brain in vivo, and Arg-108 was the major arginine methylation site. Using two different shRNAs that target Staufen1, I further demonstrated that Staufen1 was successfully knocked down in dissociated hippocampal neurons. Taken together, these results suggest that Staufen1 is methylated by PRMTs in the brain via arginine methylation at the 108th amino acid position. It will be of immense interest to further investigate how this novel form of post-translational modification on Staufen1 regulates its function in RNA transport and dendritic spine development by performing RNAi-mediated knockdown and rescue experiments.
DegreeMaster of Medical Sciences
SubjectArginine - Methylation
RNA-protein interactions
Neurons
Dept/ProgramBiomedical Sciences
Persistent Identifierhttp://hdl.handle.net/10722/221471

 

DC FieldValueLanguage
dc.contributor.authorLiao, An, Anne-
dc.contributor.author廖安-
dc.date.accessioned2015-11-26T23:35:43Z-
dc.date.available2015-11-26T23:35:43Z-
dc.date.issued2015-
dc.identifier.citationLiao, A. A. [廖安]. (2015). Characterization of arginine methylation of the RNA-binding protein Staufen in neurons. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5634738-
dc.identifier.urihttp://hdl.handle.net/10722/221471-
dc.description.abstractThe morphology and number of dendritic spines have been associated with learning and memory. Abnormality of spine morphogenesis has been found in patients suffering from cognitive disorders, such as autism. Major modulators of dendritic spines include proteins that regulate the actin cytoskeleton. Many of them are thought to be translated onsite where the dendritic spines are located, away from the nucleus of the neurons. This specificity is made possible by mRNA transcripts being transported along microtubules bound to RNA-binding proteins (RBP) forming a ribonucleoprotein complex. One of these RBPs is Staufen1, a double-stranded RNA-binding protein found ubiquitously throughout the body. Previous studies have shown that depletion of Staufen1 in neurons leads to impairment of dendritic spines and synaptic strength, but how the function of Staufen is regulated is not yet understood. Arginine methylation, catalyzed by a class of enzymes called protein arginine methyltransferases (PRMTs), is one of the key post-translational modifications that regulate protein function. The present study aims to investigate the possibility of arginine methylation as a regulatory mechanism for Staufen1. Here I found that two of the type I PRMTs, PRMT3 and PRMT8, are present in synaptoneurosome, a biochemical fraction of the brain which is enriched with synapses. Furthermore, Staufen1 was found to be arginine methylated in the brain in vivo, and Arg-108 was the major arginine methylation site. Using two different shRNAs that target Staufen1, I further demonstrated that Staufen1 was successfully knocked down in dissociated hippocampal neurons. Taken together, these results suggest that Staufen1 is methylated by PRMTs in the brain via arginine methylation at the 108th amino acid position. It will be of immense interest to further investigate how this novel form of post-translational modification on Staufen1 regulates its function in RNA transport and dendritic spine development by performing RNAi-mediated knockdown and rescue experiments.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.subject.lcshArginine - Methylation-
dc.subject.lcshRNA-protein interactions-
dc.subject.lcshNeurons-
dc.titleCharacterization of arginine methylation of the RNA-binding protein Staufen in neurons-
dc.typePG_Thesis-
dc.identifier.hkulb5634738-
dc.description.thesisnameMaster of Medical Sciences-
dc.description.thesislevelMaster-
dc.description.thesisdisciplineBiomedical Sciences-
dc.description.naturepublished_or_final_version-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats