Browsing by Author "Srinivasan Muthuswamy"

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Circular RNA and RNA binding proteins act together and regulate glioma
(Elsevier B.V., 2023) Sushree Lipsa Lopamudra Dwibedy; Mandakini Singh; Smruti Rekha Biswal; Srinivasan Muthuswamy; Ajay Kumar; Santosh Kumar
Circular RNAs, abbreviated as circRNAs, are exonuclease resistant, endogenously expressed RNA, that do not code for protein, and have a circular loop like structures with covalent closure of 5′ and 3′ ends. Plentiful circRNAs are found in eukaryotes and some of them are evolutionarily conserved. They play a crucial role in diverse cellular functions like cell division, cell cycle regulation, and gene expression. Altered expression of circRNA was observed in various diseases including several cancerous conditions and neurological disorders. Glioma is basically a type of brain tumor, which originates from neuroglia cells and metastasizes to other brain tissues. Glioblastoma is the most malignant variant of this cancer with a higher mortality rate and it is less curable as compared to other cancers. Common treatments available for this disease are chemotherapy and radiotherapy. But they have side effects that they cannot differentiate between normal cells and cancerous cells. Therefore, investigating these cancerous cells at the molecular level will be a more effective way to understand glioma, owing to the specific expression patterns of proteins along with coding and non-coding RNAs. Studies found circRNAs show differential expression in glioblastoma cells and they have diverse functions at various stages and conditions of the cell. This review discusses how circRNA and protein act together and regulate the progression of glioma by directly interacting with each other or via other indirect modes of regulation. The circRNA biomarkers of glioma can be used for diagnosis purpose and interaction between circRNA and RBP play a significant role in glioma regulation and targeting these interactions may act as a possible therapeutic strategy. © 2023
Circular RNA: A novel and potential regulator in pathophysiology of schizophrenia
(Springer, 2022) Mandakini Singh; Sushree Lipsa Lopamudra Dwibedy; Smruti Rekha Biswal; Srinivasan Muthuswamy; Ajay Kumar; Santosh Kumar
Circular RNAs (CircRNAs) are a sub-class of non-coding RNA, which are covalently closed at the ends through a non-canonical process called, backsplicing from the precursor linear RNAs. These molecules are involved in several biological phenomena including regulation of gene expression, synaptic plasticity, and cognition. Several studies have shown that circRNA are present abundantly inside the mammalian brain and they are believed to be associated with the development of neurons and neuronal functions. It is also evident that alterations in intracellular and extracellular levels of circRNAs are linked with various neurological and neuropsychiatric disorders including schizophrenia (SZ). Detailed studies of circRNAs are required to decode the molecular mechanism behind the onset of SZ and the related biological activities during disease progression. This can help unravel their role in this neurobehavioral disorder and develop effective therapeutics against the disease. The present review mainly focuses on the expression and activities of the circRNAs in the post-mortem brain, peripheral blood, and exosomes. It also gives an insight into the role of circRNA interaction with RNA binding proteins (RBPs) and nucleotide modification and their therapeutic potential in the context of schizophrenia. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Circular RNAs Binding to RNA-Binding Proteins
(Springer, 2025) Mandakini Singh; Kirthik Roshan; Srinivasan Muthuswamy; Ajay Kumar; Santosh Kumar
High-throughput RNA sequencing yields novel noncoding RNAs called circular RNAs (circRNAs). They are extensively distributed across the transcriptomes of humans and other metazoans. Research has demonstrated their critical functions in multiple cellular developmental processes and diseases, including cancer, cognitive disorders, and neurodegenerative disorders (NDDs). Aside from this, circRNAs carry out cellular functions by associating with RNA-binding proteins (RBPs) that are unique for each cell type. Given that they are a vast family of proteins, RBPs regulate gene expression through various processes like stabilization, localization, splicing, nuclear export, and RNA translation. The impact of circRNAs and the RBP complex on circRNA synthesis has become more apparent in recent years. As per new findings, circRNAs interact with RBPs and modify the way in which other RNAs and proteins operate. Numerous diseases are also linked to these relationships. Because of this, research regarding the circRNA and RBP relationship is crucial to comprehend the origins of a number of disorders. This chapter describes the newly discovered mechanisms underlying the interactions between circRNAs and RBPs as well as their functional significance in both illnesses and biological processes. © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2025.
Deciphering the RNA-binding protein interaction with the mRNAs encoded from human chromosome 15q11.2 BP1-BP2 microdeletion region
(Institute for Ionics, 2023) Smruti Rekha Biswal; Mandakini Singh; Sushree Lipsa Lopamudra Dwibedy; Subhadra Kumari; Srinivasan Muthuswamy; Ajay Kumar; Santosh Kumar
Microdeletion of the 15q11.2 BP1-BP2 region, also known as Burnside–Butler susceptibility region, is associated with phenotypes like delayed developmental language abilities along with motor skill disabilities, combined with behavioral and emotional problems. The 15q11.2 microdeletion region harbors four evolutionarily conserved and non-imprinted protein-coding genes: NIPA1, NIPA2, CYFIP1, and TUBGCP5. This microdeletion is a rare copy number variation frequently associated with several pathogenic conditions in humans. The aim of this study is to investigate the RNA-binding proteins binding with the four genes present in 15q11.2 BP1-BP2 microdeletion region. The results of this study will help to better understand the molecular intricacies of the Burnside-Butler Syndrome and also the possible involvement of these interactions in the disease aetiology. Our results of enhanced crosslinking and immunoprecipitation data analysis indicate that most of the RBPs interacting with the 15q11.2 region are involved in the post-transcriptional regulation of the concerned genes. The RBPs binding to this region are found from the in silico analysis, and the interaction of RBPs like FASTKD2 and EFTUD2 with exon-intron junction sequence of CYFIP1 and TUBGCP5 has also been validated by combined EMSA and western blotting experiment. The exon-intron junction binding nature of these proteins suggests their potential involvement in splicing process. This study may help to understand the intricate relationship of RBPs with mRNAs within this region, along with their functional significance in normal development, and lack thereof, in neurodevelopmental disorders. This understanding will help in the formulation of better therapeutic approaches. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Genetic components of microdeletion syndromes and their role in determining schizophrenia traits
(Springer Science and Business Media B.V., 2024) Smruti Rekha Biswal; Ajay Kumar; Srinivasan Muthuswamy; Santosh Kumar
Schizophrenia is a neuropsychiatric disorder characterized by various symptoms such as hallucinations, delusions, and disordered thinking. The etiology of this disease is unknown; however, it has been linked to many microdeletion syndromes that are likely to contribute to the pathology of schizophrenia. In this review we have comprehensively analyzed the role of various microdeletion syndromes, like 3q29, 15q13.3, and 22q11.2, which are known to be involved with schizophrenia. A variety of factors lead to schizophrenia phenotypes, but copy number variants that disrupt gene regulation and impair brain function and cognition are one of the causes that have been identified. Multiple case studies have shown that loss of one or more genes in the microdeletion regions lead to brain activity defects. In this article, we present a coherent paradigm that connects copy number variations (CNVs) to numerous neurological and behavioral abnormalities associated with schizophrenia. It would be helpful in understanding the different aspects of the microdeletions and how they contribute in the pathophysiology of schizophrenia. © The Author(s), under exclusive licence to Springer Nature B.V. 2024.