المؤلفون: Kadumuri, Rajashekar Varma¹, Janga, Sarath Chandra^1,2,3 scjanga@iupui.edu

المصدر: Trends in Molecular Medicine. Oct2018, Vol. 24 Issue 10, p886-903. 18p.

مصطلحات موضوعية: *RNA modification & restriction, *GENE regulatory networks, *RNA interference, *RNA metabolism, *IMMUNOGLOBULINS

مستخلص: Innovations in epitranscriptomics have resulted in the identification of more than 160 RNA modifications to date. These developments, together with the recent discovery of writers, readers, and erasers of modifications occurring across a wide range of RNAs and tissue types, have led to a surge in integrative approaches for transcriptome-wide mapping of modifications and protein–RNA interaction profiles of epitranscriptome players. RNA modification maps and crosstalk between them have begun to elucidate the role of modifications as signaling switches, entertaining the notion of an epitranscriptomic code as a driver of the post-transcriptional fate of RNA. Emerging single-molecule sequencing technologies and development of antibodies specific to various RNA modifications could enable charting of transcript-specific epitranscriptomic marks across cell types and their alterations in disease. Highlights A literature survey on RNA modifications reveals that RNA modifications are abundant in tRNAs, rRNAs, snoRNAs, and snRNAs but that their diversity is prominent in tRNAs, rRNAs, and mRNAs followed by snRNAs and snoRNAs. Increasing evidence provides a link between RNA modifications and post-transcriptional regulatory processes. Gene knockout and functional studies report the importance of RNA modifications in human health and disease. Emerging long read direct RNA sequencing technologies and development of antibodies specific to RNA modifications could be promising venues for charting the combinatorial epitranscriptomic code across cell types. Locus- and cell-type-specific combinations of epitranscriptome marks could drive the post-transcriptional regulatory fate of an RNA molecule. [ABSTRACT FROM AUTHOR]

المؤلفون: Kadumuri, Rajashekar Varma, Vadrevu, Ramakrishna

المصدر: Journal of Computational Biology. Oct2017, Vol. 24 Issue 10, p1043-1049. 7p.

مصطلحات موضوعية: *PROTEIN structure, *COMPUTATIONAL biology, *PROTEIN folding, *GRAPHICAL user interfaces, *HYDROGEN bonding, *PROTEIN conformation

مستخلص: Due to their crucial role in function, folding, and stability, protein loops are being targeted for grafting/designing to create novel or alter existing functionality and improve stability and foldability. With a view to facilitate a thorough analysis and effectual search options for extracting and comparing loops for sequence and structural compatibility, we developed, LoopX a comprehensively compiled library of sequence and conformational features of ∼700,000 loops from protein structures. The database equipped with a graphical user interface is empowered with diverse query tools and search algorithms, with various rendering options to visualize the sequence- and structural-level information along with hydrogen bonding patterns, backbone φ, ψ dihedral angles of both the target and candidate loops. Two new features (i) conservation of the polar/nonpolar environment and (ii) conservation of sequence and conformation of specific residues within the loops have also been incorporated in the search and retrieval of compatible loops for a chosen target loop. Thus, the LoopX server not only serves as a database and visualization tool for sequence and structural analysis of protein loops but also aids in extracting and comparing candidate loops for a given target loop based on user-defined search options. [ABSTRACT FROM AUTHOR]

المؤلفون: Kadumuri, Rajashekar Varma¹, Gullipalli, Jagadeesh¹, Subramanian, SriVidya¹, Jaipuria, Garima², Atreya, Hanudatta S.², Vadrevu, Ramakrishna¹

المصدر: FEBS Letters. Jul2016, Vol. 590 Issue 14, p2096-2105. 10p.

مصطلحات موضوعية: *TRYPTOPHAN synthase, *FICOLL, *CIRCULAR dichroism, *FLUORESCENCE spectroscopy, *DENATURATION of proteins, *NUCLEAR magnetic resonance

مستخلص: The consequences of crowding derived from relatively small and intrinsically disordered proteins are not clear yet. We report the effect of ficoll-70 on the structure and stability of native and partially folded states of the 29 kDa alpha subunit of tryptophan synthase (α TS). Overall, combining the changes in the circular dichroism and fluorescence spectra, in conjunction with the gradual loss of cooperativity under urea denaturation in the presence of increasing amounts of ficoll, it may be concluded that the crowding agent perturbs not only the native state but also the partially folded state of α TS. Importantly, NMR data indicate that ficoll interacts with the residues that constitute the stable core of the protein thus shedding light on the origin of the observed perturbation. [ABSTRACT FROM AUTHOR]

المؤلفون: Gupta, Somlee¹ (AUTHOR) somleegupta@gmail.com, Kadumuri, Rajashekar Varma² (AUTHOR) rajashekar@labs.iisertirupati.ac.in, Singh, Anjali Kumari² (AUTHOR) anjaliksingh@students.iisertirupati.ac.in, Chavali, Sreenivas² (AUTHOR) schavali@iisertirupati.ac.in, Dhayalan, Arunkumar¹ (AUTHOR) arun.dbt@pondiuni.edu.in

المصدر: Life (2075-1729). Sep2021, Vol. 11 Issue 9, p951. 1p.

مصطلحات موضوعية: *PROTEIN arginine methyltransferases, *CELL physiology, *GENETIC regulation, *METHYLTRANSFERASES, *ENZYME kinetics, *PROTEINS

مستخلص: Members of the protein arginine methyltransferase (PRMT) family methylate the arginine residue(s) of several proteins and regulate a broad spectrum of cellular functions. Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that asymmetrically dimethylates the arginine residues of numerous substrate proteins. PRMT6 introduces asymmetric dimethylation modification in the histone 3 at arginine 2 (H3R2me2a) and facilitates epigenetic regulation of global gene expression. In addition to histones, PRMT6 methylates a wide range of cellular proteins and regulates their functions. Here, we discuss (i) the biochemical aspects of enzyme kinetics, (ii) the structural features of PRMT6 and (iii) the diverse functional outcomes of PRMT6 mediated arginine methylation. Finally, we highlight how dysregulation of PRMT6 is implicated in various types of cancers and response to viral infections. [ABSTRACT FROM AUTHOR]

المؤلفون: Govindaraju, Gayathri^1,2 (AUTHOR), Kadumuri, Rajashekar Varma³ (AUTHOR), Sethumadhavan, Devadathan Valiyamangalath^1,2 (AUTHOR), Jabeena, C. A.^1,2 (AUTHOR), Chavali, Sreenivas³ (AUTHOR), Rajavelu, Arumugam¹ (AUTHOR) arajavelu@rgcb.res.in

المصدر: Epigenetics & Chromatin. 9/22/2020, Vol. 13 Issue 1, pN.PAG-N.PAG. 1p.

مصطلحات موضوعية: *PLASMODIUM falciparum, *PLASMODIUM, *PROTEIN domains, *METHYLATION, *MESSENGER RNA

مستخلص: An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

المؤلفون: Govindaraju, Gayathri^1,2 (AUTHOR), Kadumuri, Rajashekar Varma³ (AUTHOR), Sethumadhavan, Devadathan Valiyamangalath^1,2 (AUTHOR), Jabeena, C. A.^1,2 (AUTHOR), Chavali, Sreenivas³ (AUTHOR), Rajavelu, Arumugam¹ (AUTHOR) arajavelu@rgcb.res.in

المصدر: Epigenetics & Chromatin. 8/31/2020, Vol. 13 Issue 1, pN.PAG-N.PAG. 1p.

مصطلحات موضوعية: *PLASMODIUM falciparum, *PROTEIN domains, *PLASMODIUM, *MESSENGER RNA, *MOLECULAR dynamics, *METHYLATION

مستخلص: Background: Plasmodium falciparum exhibits high translational plasticity during its development in RBCs, yet the regulation at the post-transcriptional level is not well understood. The N6-methyl adenosine (m6A) is an important epigenetic modification primarily present on mRNA that controls the levels of transcripts and efficiency of translation in eukaryotes. Recently, the dynamics of m6A on mRNAs at all three developmental stages of P. falciparum in RBCs have been profiled; however, the proteins that regulate the m6A containing mRNAs in the parasites are unknown. Results: Using sequence analysis, we computationally identified that the P. falciparum genome encodes two putative YTH (YT521-B Homology) domain-containing proteins, which could potentially bind to m6A containing mRNA. We developed a modified methylated RNA immunoprecipitation (MeRIP) assay using PfYTH2 and find that it binds selectively to m6A containing transcripts. The PfYTH2 has a conserved aromatic amino acid cage that forms the methyl-binding pocket. Through site-directed mutagenesis experiments and molecular dynamics simulations, we show that F98 residue is important for m6A binding on mRNA. Fluorescence depolarization assay confirmed that PfYTH2 binds to methylated RNA oligos with high affinity. Further, MeRIP sequencing data revealed that PfYTH2 has more permissive sequence specificity on target m6A containing mRNA than other known eukaryotic YTH proteins. Taken together, here we identify and characterize PfYTH2 as the major protein that could regulate m6A containing transcripts in P. falciparum. Conclusion: Plasmodium spp. lost the canonical m6A-specific demethylases in their genomes, however, the YTH domain-containing proteins seem to be retained. This study presents a possibility that the YTH proteins are involved in post-transcriptional control in P. falciparum, and might orchestrate the translation of mRNA in various developmental stages of P. falciparum. This is perhaps the first characterization of the methyl-reading function of YTH protein in any parasites. [ABSTRACT FROM AUTHOR]

المؤلفون: Verma, Mamta¹, Khan, Mohd. Imran K.¹, Kadumuri, Rajashekar Varma², Chakrapani, Baskar¹, Awasthi, Sharad¹, Mahesh, Arun¹, Govindaraju, Gayathri³, Chavali, Pavithra L⁴, Rajavelu, Arumugam³, Chavali, Sreenivas² schavali@iisertirupati.ac.in, Dhayalan, Arunkumar¹ arun.dbt@pondiuni.edu.in

المصدر: Communications Biology. 1/25/2021, Vol. 4 Issue 1, p1-15. 15p.

مصطلحات موضوعية: *RETINOIC acid receptors, *PROTEIN arginine methyltransferases, *PROTEIN-protein interactions, *GENE expression in mammals, *DNA methylation, *MOLECULAR docking

مستخلص: Protein arginine methyltransferase 3 (PRMT3) regulates protein functions by introducing asymmetric dimethylation marks at the arginine residues in proteins. However, very little is known about the interaction partners of PRMT3 and their functional outcomes. Using yeast-two hybrid screening, we identified Retinal dehydrogenase 1 (ALDH1A1) as a potential interaction partner of PRMT3 and confirmed this interaction using different methods. ALDH1A1 regulates variety of cellular processes by catalyzing the conversion of retinaldehyde to retinoic acid. By molecular docking and site-directed mutagenesis, we identified the specific residues in the catalytic domain of PRMT3 that facilitate interaction with the C-terminal region of ALDH1A1. PRMT3 inhibits the enzymatic activity of ALDH1A1 and negatively regulates the expression of retinoic acid responsive genes in a methyltransferase activity independent manner. Our findings show that in addition to regulating protein functions by introducing methylation modifications, PRMT3 could also regulate global gene expression through protein-protein interactions. Here, the authors demonstrate that protein arginine methyltransferase 3 (PRMT3) interacts with and inhibits the retinal dehydrogenase ALDH1A1, negatively regulating the expression of retinoic acid responsive genes. This study shows that PRMT3 affects diverse biological processes not only by globally regulating protein function through methylation but also by regulating gene expression. [ABSTRACT FROM AUTHOR]

المؤلفون: Samantaray, Devidutta¹ (AUTHOR), Vankanavath, Aruna Bai¹ (AUTHOR), Kadumuri, Rajashekar Varma¹ (AUTHOR), Ramadurai, Dhanya¹ (AUTHOR), Chavali, Sreenivas¹ (AUTHOR), Allu, Annapurna Devi¹ (AUTHOR) anu.allu@iisertirupati.ac.in

المصدر: Environmental & Experimental Botany. Jul2023, Vol. 211, pN.PAG-N.PAG. 1p.

مصطلحات موضوعية: *BRASSICA juncea, *HEAT shock factors, *OILSEED plants, *SEED crops, *OILSEEDS, *VEGETABLE oils

مستخلص: Brassica juncea (also known as Indian mustard) is an important vegetable oil seed crop whose growth and productivity is severely affected by heat stress. Interestingly, pre-exposure to sublethal heat stress, referred as thermopriming can remarkably enhance the plant heat stress tolerance. However, little is known about the impact of thermopriming on heat stress response of the important oil seed crop, B. juncea. In this study, we investigated the basal and thermopriming-induced heat stress response of 16 different cultivated, agronomically important varieties of Brassica juncea. Based on their basal heat stress response, we classify the varieties as heat sensitive, moderately tolerant or tolerant. Notably, almost all the varieties displayed enhanced heat stress tolerance upon thermopriming (acquired thermotolerance), albeit to varying magnitudes. Strikingly, the high oil-yielding, drought tolerant, heat sensitive variety Pusa Bold showed remarkable acquired thermotolerance upon thermopriming. Investigations in Pusa Bold indicate that the thermopriming-induced acquired thermotolerance predominantly correlates with the rapid activation of ROS scavenging mechanisms and differential expression of Heat Shock Family of transcription factors (BjHSF s). Taken together, our study reveals the positive impact of thermopriming in alleviating the harmful effects of heat stress on Brassica juncea seedlings and paves the path to enhance heat stress tolerance for improved productivity in the important oilseed crop Indian mustard. [Display omitted] • Heat stress affects the survivability of different varieties of Indian mustard. • Thermopriming provides acquired thermotolerance even in heat-sensitive varieties. • Thermopriming regulates ROS homeostasis and the expression of heat shock factors. [ABSTRACT FROM AUTHOR]

المؤلفون: Chutani, Namita¹ (AUTHOR), Singh, Anjali Kumari¹ (AUTHOR), Kadumuri, Rajashekar Varma¹ (AUTHOR), Pakala, Suresh B.¹ (AUTHOR) pakalasb@iisertirupati.ac.in, Chavali, Sreenivas¹ (AUTHOR) schavali@iisertirupati.ac.in

المصدر: Journal of Molecular Biology. Jul2022, Vol. 434 Issue 14, pN.PAG-N.PAG. 1p.

مصطلحات موضوعية: *PROTEIN-protein interactions, *MOLECULAR interactions, *MITOCHONDRIA, *CHROMATIN, *COMPACTING, *DIMERIZATION

مستخلص: [Display omitted] • MORCs are involved in chromatin relaxation and compaction. • ATP binding is essential for MORC dimerization and catalytic function. • MORCs participate in condensates and could regulate their formation/function. • MORCs localise to cytoplasm and mitochondria and might have extra-nuclear roles. • Dysfunction/dysregulation of MORCs is linked with various diseases. Chromatin remodelers affect the spatio-temporal dynamics of global gene-expression by structurally modulating and/or reorganizing the chromatin. Microrchidia (MORC) family is a relatively new addition to the four well studied families of chromatin remodeling proteins. In this review, we discuss the current understanding of the structural aspects of human MORCs as well as their epigenetic functions. From a molecular and systems-level perspective, we explore their participation in phase-separated structures, possible influence on various biological processes through protein–protein interactions, and potential extra-nuclear roles. We describe how dysregulation/dysfunction of MORCs can lead to various pathological conditions. We conclude by emphasizing the importance of undertaking integrated efforts to obtain a holistic understanding of the various biological roles of MORCs. [ABSTRACT FROM AUTHOR]