Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Article Citation - WoS: 14Citation - Scopus: 16Plaqview 2.0: a Comprehensive Web Portal for Cardiovascular Single-Cell Genomics(Frontiers Media S.A., 2022) Ma, Wei Feng; Turner, Adam W.; Gancayco, Christina; Wong, Doris; Song, Yipei; Mosquera, Jose Verdezoto; Auguste, Gaëlle; Hodonsky, Chani J.; Prabhakar, Ajay; Ekiz, Hüseyin Atakan; van der Laan, Sander W.; Miller, Clint L.Single-cell RNA-seq (scRNA-seq) is a powerful genomics technology to interrogate the cellular composition and behaviors of complex systems. While the number of scRNA-seq datasets and available computational analysis tools have grown exponentially, there are limited systematic data sharing strategies to allow rapid exploration and re-analysis of single-cell datasets, particularly in the cardiovascular field. We previously introduced PlaqView, an open-source web portal for the exploration and analysis of published atherosclerosis single-cell datasets. Now, we introduce PlaqView 2.0 (www.plaqview.com), which provides expanded features and functionalities as well as additional cardiovascular single-cell datasets. We showcase improved PlaqView functionality, backend data processing, user-interface, and capacity. PlaqView brings new or improved tools to explore scRNA-seq data, including gene query, metadata browser, cell identity prediction, ad hoc RNA-trajectory analysis, and drug-gene interaction prediction. PlaqView serves as one of the largest central repositories for cardiovascular single-cell datasets, which now includes data from human aortic aneurysm, gene-specific mouse knockouts, and healthy references. PlaqView 2.0 brings advanced tools and high-performance computing directly to users without the need for any programming knowledge. Lastly, we outline steps to generalize and repurpose PlaqView's framework for single-cell datasets from other fields.Article Citation - WoS: 6Citation - Scopus: 6Analysis of Brain Lipids in the Early-Onset Tay–sachs Disease Mouse Model With the Combined Deficiency of Β-Hexosaminidase a and Neuraminidase 3(Frontiers Media S.A., 2022) Can, Melike; Şengül, Tuğçe; Akyıldız Demir, Seçil; İnci, Orhan K.; Basırlı, Hatice Hande; Seyrantepe, VolkanTay–Sachs disease is an autosomal recessively inherited lysosomal storage disease that results from loss-of-function mutations in the HEXA gene coding βhexosaminidase A. HEXA gene deficiency affects the central nervous system owing to GM2 ganglioside accumulation in lysosomes resulting in progressive neurodegeneration in patients. We recently generated a novel mice model with a combined deficiency of βhexosaminidase A and neuraminidase 3 (Hexa−/−Neu3−/−) that mimics both the neuropathological and clinical abnormalities of early-onset Tay–Sachs disease. Here, we aimed to explore the secondary accumulation of lipids in the brain of Hexa−/ −Neu3−/− mice.Article Citation - WoS: 19Citation - Scopus: 24Intracytoplasmic Re-Localization of Mirisc Complexes(Frontiers Media S.A., 2018) Akgül, Bünyamin; Erdoğan, İpekMicroRNAs (miRNAs) are a conserved class of non-coding RNAs of 22 nucleotides that post-transcriptionally regulate gene expression through translational repression and/or mRNA degradation. A great progress has been made regarding miRNA biogenesis and miRNA-mediated gene regulation. Additionally, an ample amount of information exists with respect to the regulation of miRNAs. However, the cytoplasmic localization of miRNAs and its effect on gene regulatory output is still in progress. We provide a current review of the cytoplasmic miRNA localization in metazoans. We then discuss the dynamic changes in the intracytoplasmic localization of miRNAs as a means to regulate their silencing activity. We then conclude our discussion with the potential molecules that could modulate miRNA localization.Article Citation - WoS: 28Citation - Scopus: 31Lysosomal Cathepsin a Plays a Significant Role in the Processing of Endogenous Bioactive Peptides(Frontiers Media S.A., 2016) Timur, Zehra Kevser; Akyıldız Demir, Seçil; Seyrantepe, VolkanLysosomal serine carboxypeptidase Cathepsin A (CTSA) is a multifunctional enzyme with distinct protective and catalytic function. CTSA present in the lysosomal multienzyme complex to facilitate the correct lysosomal routing, stability and activation of with beta-galactosidase and alpha-neuraminidase. Beside CTSA has role in inactivation of bioactive peptides including bradykinin, substances P, oxytocin, angiotensin I and endothelin-I by cleavage of 1 or 2 amino acid(s) from C-terminal ends. In this study, we aimed to elucidate the regulatory role of CTSA on bioactive peptides in knock-in mice model of CTSA(S190A). We investigated the level of bradykinin, substances P, oxytocin, angiotensin I and endothelin-I in the kidney, liver, lung, brain and serum from CTSA(S190A) mouse model at 3- and 6-months of age. Our results suggest CTSA selectively contributes to processing of bioactive peptides in different tissues from CTSA(S190A) mice compared to age matched WT mice.Article Citation - WoS: 11Citation - Scopus: 13Transcriptomics Analysis of Circular Rnas Differentially Expressed in Apoptotic Hela Cells(Frontiers Media S.A., 2019) Yaylak, Bilge; Erdoğan, İpek; Akgül, BünyaminApoptosis is a form of regulated cell death that plays a critical role in survival and developmental homeostasis. There are numerous reports on regulation of apoptosis by protein-coding genes as well as small non-coding RNAs, such as microRNAs. However, there is no comprehensive investigation of circular RNAs (circRNA) that are differentially expressed under apoptotic conditions. We have performed a transcriptomics study in which we first triggered apoptosis in HeLa cells through treatment with four different agents, namely cisplatin, doxorubicin, TNF-alpha and anti-Fas mAb. Total RNAs isolated from control as well as treated cells were treated with RNAse R to eliminate the linear RNAs. The remaining RNAs were then subjected to deep-sequencing to identify differentially expressed circRNAs. Interestingly, some of the dys-regulated circRNAs were found to originate from protein-coding genes well-documented to regulate apoptosis. A number of candidate circRNAs were validated with qPCR with or without RNAse R treatment as well. We then took advantage of bioinformatics tools to investigate the coding potential of differentially expressed RNAs. Additionally, we examined the candidate circRNAs for the putative miRNA-binding sites and their putative target mRNAs. Our analyses point to a potential for circRNA-mediated sponging of miRNAs known to regulate apoptosis. In conclusion, this is the first transcriptomics study that provides a complete circRNA profile of apoptotic cells that might shed light onto the potential role of circRNAs in apoptosis.Article Citation - WoS: 66Citation - Scopus: 71Lithium Protects Against Paraquat Neurotoxicity by Nrf2 Activation and Mir-34a Inhibition in Sh-Sy5y Cells(Frontiers Media S.A., 2015) Alural, Begüm; Özerdem, Ayşegül; Allmer, Jens; Genç, Kürşad; Genç, ŞerminLithium is a mood stabilizing agent commonly used for the treatment of bipolar disorder. Here, we investigated the potential neuroprotective effect of lithium against paraquat toxicity and its underlying mechanisms in vitro. SH-SY5Y human neuroblastoma cells were treated with paraquat (PQ) 0.5 mM concentration after lithium pretreatment to test lithium's capability in preventing cell toxicity. Cell death was evaluated by LDH, WST-8, and tryphan blue assays. Apoptosis was analyzed using DNA fragmentation, Annexin V immunostaining, Sub G1 cell cycle analysis, and caspase-3 activity assays. BCL2, BAX, and NRF2 protein expression were evaluated by Western-blotting and the BDNF protein level was determined with ELISA. mRNA levels of BCL2, BAX, BDNF, and NRF2 target genes (HO-1, GCS, NQO1), as well as miR-34a expression were analyzed by qPCR assay. Functional experiments were done via transfection with NRF2 siRNA and miR-34a mimic. Lithium treatment prevented paraquat induced cell death and apoptosis. Lithium treated cells showed increased anti-apoptotic protein BCL2 and decreased pro-apoptotic protein BAX expression. Lithium exerted a neurotrophic effect by increasing BDNF protein expression. It also diminished reactive oxygen species production and activated the redox sensitive transcription factor NRF2 and increased its target genes expression. Knockdown of NRF2 abolished neuroprotective, anti-apoptotic, and anti-oxidant effects of lithium. Furthermore, lithium significantly decreased both basal and PQ-induced expression of miR-34a. Transfection of miR-34a specific mimic reversed neuroprotective, anti-apoptotic, and anti-oxidant effects of lithium against PQ-toxicity. Our results revealed two novel mechanisms of lithium neuroprotection, namely NRF2 activation and miR-34a suppression.Article Citation - Scopus: 29Computational Methods for Ab Initio Detection of Micrornas(Frontiers Media S.A., 2012) Allmer, Jens; Yousef, MalikMicroRNAs are small RNA sequences of 18-24 nucleotides in length, which serve as templates to drive post-transcriptional gene silencing. The canonical microRNA pathway starts with transcription from DNA and is followed by processing via the microprocessor complex, yielding a hairpin structure. Which is then exported into the cytosol where it is processed by Dicer and then incorporated into the RNA-induced silencing complex. All of these biogenesis steps add to the overall specificity of miRNA production and effect. Unfortunately, their modes of action are just beginning to be elucidated and therefore computational prediction algorithms cannot model the process but are usually forced to employ machine learning approaches. This work focuses on ab initio prediction methods throughout; and therefore homology-based miRNA detection methods are not discussed. Current ab initio prediction algorithms, their ties to data mining, and their prediction accuracy are detailed.