Plasmodium falciparum Tudor Staphylococcal Nuclease interacting proteins suggest its role in nuclear as well as splicing processes

Hossain, Manzar; Korde, Reshma; Singh, Prashant; Kanodia, Shivani; Ranjan, Ravi; Ram, Geeta; Kalsey, Gaganjot Singh; Singh, Rita; Malhotra, Pawan

doi:10.1016/j.gene.2010.08.004

Cited by 23 publications

(20 citation statements)

References 44 publications

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“…An interaction between recombinant PfTu-TSN and PfSmD1 proteins has also been reported earlier [48]. To know the involvement of PfSMN protein with the Plasmodium spliceosome assembly, PfSMN protein was expressed and purified as a GST-fusion protein (Figure 4A (i)).…”

Section: Resultssupporting

confidence: 66%

“…In human, Tu-TSN and Tudor domain of SMN have been shown to interact with symmetrically dimethylated SmB as well as SmD1/D3 proteins and these interactions are essential for the snRNP assembly [57]. An earlier report has described two Tudor domain -containing proteins; PfTSN and PfSMN in P. falciparum [48]. In the present study, their interactions with PfSm proteins were evaluated.…”

Section: Discussionmentioning

confidence: 99%

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Organization of Plasmodium falciparum spliceosomal core complex and role of arginine methylation in its assembly

Hossain

Sharma

Korde

et al. 2013

Malar J

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BackgroundSplicing and alternate splicing are the two key biological processes that result in the generation of diverse transcript and protein isoforms in Plasmodium falciparum as well as in other eukaryotic organisms. Not much is known about the organization of splicing machinery and mechanisms in human malaria parasite. Present study reports the organization and assembly of Plasmodium spliceosome Sm core complex.MethodsPresence of all the seven Plasmodium Sm-like proteins in the intra-erythrocytic stages was assessed based on the protein(s) expression analysis using immuno-localization and western blotting. Localization/co-localization studies were performed by immunofluorescence analysis on thin parasite smear using laser scanning confocal microscope. Interaction studies were carried out using yeast two-hybrid analysis and validated by in vitro pull-down assays. PfPRMT5 (arginine methyl transferase) and PfSmD1 interaction analysis was performed by pull-down assays and the interacting proteins were identified by MALDI-TOF spectrometry.ResultsPfSm proteins are expressed at asexual blood stages of the parasite and show nucleo-cytoplasmic localization. Protein-protein interaction studies showed that PfSm proteins form a heptameric complex, typical of spliceosome core complex as shown in humans. Interaction of PfSMN (survival of motor neuron, tudor domain containing protein) or PfTu-TSN (Tudor domain of Tudor Staphylococcal nuclease) with PfSmD1 proteins was found to be methylation dependent. Co-localization by immunofluorescence and co-immunoprecipitation studies suggested an association between PfPRMT5 and PfSmD1, indicating the role of arginine methylation in assembly of Plasmodium spliceosome complex.ConclusionsPlasmodium Sm-like proteins form a heptameric ring-like structure, although the arrangement of PfSm proteins slightly differs from human splicing machinery. The data shows the interaction of PfSMN with PfSmD1 and this interaction is found to be methylation dependent. PfPRMT5 probably exists as a part of methylosome complex that may function in the cytoplasmic assembly of Sm proteins at asexual blood stages of P. falciparum.

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Section: Resultssupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Organization of Plasmodium falciparum spliceosomal core complex and role of arginine methylation in its assembly

Hossain

Sharma

Korde

et al. 2013

Malar J

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“…[30][31][32] The interaction of Tudor domain with SmD1, a Sm protein from Plasmodium falciparum suggests an evolutionary conserved role of TSN in splicing. 33 The interaction with PIWIL1/Miwi, a specific member of the Argonaute family, suggests a role for TSN in the biogenesis of noncoding RNAs in mammals. 25,34 Because of the cross-kingdom conservation of TSN sequence and its molecular structure, this protein might perform similar functions in different organisms.…”

Section: Structure and Intracellular Localization Of Tsn: Clues To Mumentioning

confidence: 99%

“…Although the function of TSN as transcriptional co-activator has been only described in human cells, a yeast two-hybrid analysis performed in the malaria parasite P. falciparum suggested, albeit not proved exclusively, a similar role for TSN in protozoa. 33 Pim-1 is a serine/threonine protein kinase that cooperates with c-Myc during lymphoid cell transformation in human. Leverson et al 39 revealed that Pim-1 phosphorylates TSN forming a stable complex, which promotes transcriptional activity of c-Myb in a TSN-dependent manner.…”

Section: Structure and Intracellular Localization Of Tsn: Clues To Mumentioning

confidence: 99%

“…30 A recent finding that P. falciparum TSN interacts with SmD1 protein suggests that the role of TSN in pre-mRNA splicing may also be conserved between protozoa and animals. 33 Misregulation of splicing contributes to an increasing number of human pathologies, including genetic and neurodegenerative diseases, as well as cancer. 52 These disorders can be caused by mutations that disrupt splicing of specific genes or by a general loss of a spliceosomal function affecting entire networks of downstream genes.…”

Section: Role Of Tsn In Splicingmentioning

confidence: 99%

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Tudor staphylococcal nuclease: biochemistry and functions

et al. 2016

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Tudor staphylococcal nuclease (TSN, also known as Tudor-SN, SND1 or p100) is an evolutionarily conserved protein with invariant domain composition, represented by tandem repeat of staphylococcal nuclease domains and a tudor domain. Conservation along significant evolutionary distance, from protozoa to plants and animals, suggests important physiological functions for TSN. It is known that TSN is critically involved in virtually all pathways of gene expression, ranging from transcription to RNA silencing. Owing to its high protein-protein binding affinity coexistent with enzymatic activity, TSN can exert its biochemical function by acting as both a scaffolding molecule of large multiprotein complexes and/or as a nuclease. TSN is indispensible for normal development and stress resistance, whereas its increased expression is closely associated with various types of cancer. Thus, TSN is an attractive target for anti-cancer therapy and a potent tumor marker. Considering ever increasing interest to further understand a multitude of TSN-mediated processes and a mechanistic role of TSN in these processes, here we took an attempt to summarize and update the available information about this intriguing multifunctional protein. TSN is an evolutionarily conserved protein having a pivotal role in the regulation of gene expression. TSN acts both as a scaffolding protein and as a nuclease. TSN sustains cell viability and its cleavage by proteases facilitates cell death. TSN is implicated in key cancer-related processes and is a potent marker of various types of tumors. Open questions:How is nucleolytic activity of TSN regulated in vivo and how this affects interaction of TSN with downstream targets? What are the structural bases and functional consequences of distinct intracellular localization patterns of TSN in animals and plants? What are the molecular mechanisms of the TSN-mediated cancerogenesis?God has given you one face, and you make yourself another (William Shakespeare). Being true for all living organisms, accurate spatio-temporal regulation of gene expression is a fundamental mechanism underlying development, homeostasis and adaptation to the environment. Eukaryotic gene expression is a cumulative outcome of a multitude of molecular processes, including transcription, mRNA splicing, stability and translation, chromatin modification, as well as protein stability and modification. Each of these processes is in turn controlled by a highly dedicated repertoire of proteins. However, one protein, Tudor staphylococcal nuclease (TSN, also known as Tudor-SN, SND1 or p100) appears to act in most of the gene expression pathways.TSN is an evolutionarily conserved protein found in all eukaryotic lineages, except budding yeast, Saccharomyces cerevisiae. Conservation along significant evolutionary distance suggests important physiological functions for TSN. Invariant domain composition of TSN comprises tandem repeat of four staphylococcal nuclease (SN)-like domains (hereafter referred to as SN domains) at the N terminus and a fusio...

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