Interaction of tau with HNRNPA2B1 and N6-methyladenosine RNA mediates the progression of tauopathy.

The microtubule-associated protein tau oligomerizes, but the actions of oligomeric tau (oTau) are unknown. We have used Cry2-based optogenetics to induce tau oligomers (oTau-c). Optical induction of oTau-c elicits tau phosphorylation, aggregation, and a translational stress response that includes stress granules and reduced protein synthesis. Proteomic analysis identifies HNRNPA2B1 as a principle target of oTau-c. The association of HNRNPA2B1 with endogenous oTau was verified in neurons, animal models, and human Alzheimer brain tissues. Mechanistic studies demonstrate that HNRNPA2B1 functions as a linker, connecting oTau with N6-methyladenosine (m6A) modified RNA transcripts. Knockdown of HNRNPA2B1 prevents oTau or oTau-c from associating with m6A or from reducing protein synthesis and reduces oTau-induced neurodegeneration. Levels of m6A and the m6A-oTau-HNRNPA2B1 complex are increased up to 5-fold in the brains of Alzheimer subjects and P301S tau mice. These results reveal a complex containing oTau, HNRNPA2B1, and m6A that contributes to the integrated stress response of oTau.

Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2.

Human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative pathogen of the COVID-19 pandemic, exerts a massive health and socioeconomic crisis. The virus infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange, but the mechanisms driving infection and pathology are unclear. We performed a quantitative phosphoproteomic survey of induced pluripotent stem cell-derived AT2s (iAT2s) infected with SARS-CoV-2 at air-liquid interface (ALI). Time course analysis revealed rapid remodeling of diverse host systems, including signaling, RNA processing, translation, metabolism, nuclear integrity, protein trafficking, and cytoskeletal-microtubule organization, leading to cell cycle arrest, genotoxic stress, and innate immunity. Comparison to analogous data from transformed cell lines revealed respiratory-specific processes hijacked by SARS-CoV-2, highlighting potential novel therapeutic avenues that were validated by a high hit rate in a targeted small molecule screen in our iAT2 ALI system.

DDX49 is an RNA helicase that affects translation by regulating mRNA export and the levels of pre-ribosomal RNA.

Among the proteins predicted to be a part of the DExD box RNA helicase family, the functions of DDX49 are unknown. Here, we characterize the enzymatic activities and functions of DDX49 by comparing its properties with the well-studied RNA helicase, DDX39B. We find that DDX49 exhibits a robust ATPase and RNA helicase activity, significantly higher than that of DDX39B. DDX49 is required for the efficient export of poly (A)+ RNA from nucleus in a splicing-independent manner. Furthermore, DDX49 is a resident protein of nucleolus and regulates the steady state levels of pre-ribosomal RNA by regulating its transcription and stability. These dual functions of regulating mRNA export and pre-ribosomal RNA levels enable DDX49 to modulate global translation. Phenotypically, DDX49 promotes proliferation and colony forming potential of cells. Strikingly, DDX49 is significantly elevated in diverse cancer types suggesting that the increased abundance of DDX49 has a role in oncogenic transformation of cells. Taken together, this study shows the physiological role of DDX49 in regulating distinct steps of mRNA and pre-ribosomal RNA metabolism and hence translation and potential pathological role of its dysregulation, especially in cancers.

The Pathophysiology of Tau and Stress Granules in Disease.

This chapter discusses the relationship between tau, RNA binding proteins and stress granules, which exhibit an intimate bidirectional relationship affecting the functions of both tau and the translational stress response. We describe how tau becomes hyperphosphorylated and oligomerized as part of an endogenous mechanism to promote the translational stress response through interaction with RNA binding proteins. Prior studies demonstrate that dysfunction of RNA binding proteins biology is sufficient to cause neurodegenerative diseases, such as amyotrophic lateral sclerosis and frontotemporal dementia. Emerging evidence indicates that tau-mediated neurodegeneration also occurs through a mechanism that is mediated by RNA binding proteins and the translational stress response. Discovery of the role of RNA metabolism in tauopathy opens a wide variety of novel therapeutic approaches. Multiple studies have already shown that approaches reducing the levels of selected RNA binding proteins or inhibiting the translational stress response can intervene in the pathophysiology of motoneuron diseases. Emerging studies show that reducing the levels of selected RNA binding proteins or inhibiting the translational stress response also reduces neurodegeneration in models of tauopathy and Aß mediated degeneration. The combined impact of these studies indicate that RNA binding proteins and RNA metabolism represent a valuable new frontier for the investigation and treatment tauopathies.

Honey infused with herbs: A boon to cure pathological diseases.

Healing with herbs has been a common practice for ages. Nowadays, various infectious diseases like malaria, flu, hepatitis B; COVID-19, etc. are commonly spreading around the world as a consequence of environmental pollution and related consequences. These diseases are not well controlled by the present drug treatment. Antibiotics are failing because of bacterial resistance. Although people believe that herbal medicines are more effective and safer. Therefore, traditional herbal remedies have been recommended for treatment purposes throughout the world. They are often used in combination, fused with honey, or alone for curing different types of ailments. Today, modern formulations of these medicines exist in the form of capsules, tablets, powders, and granules. In several traditional systems, 'Honey' is recommended as a natural medicine that improves several health conditions. In 'Ayurveda', honey is considered a most precious and miraculous product of nature and is used to treat various diseases either alone or after its infusion with herbs. It is a natural, antioxidant-rich, and highly nutritious food that is widely used as a natural sweetener without any side effects. It has antibacterial, antiviral, antifungal, and antioxidant properties. It also proves fruitful in managing/curing various disorders like colds, coughs, cancer, diabetes, wound healing, and cardiovascular disorders. Honey infused with herbs is also used to repair wounds, diabetes, lymphedema, and the prevention of chronic venomous diseases as a part of the folk medicinal system. The current article aims to analyse the medicinal efficiency of honey infused with herbs for curing/managing/treating various types of ailments.

Preferences and factors determining preferences for mode of delivery among primigravida mothers.

Background: Childbirth is a beautiful life event, a unique personal experience for each woman. The study aimed to assess the preferences and factors determining preference for mode of delivery among primigravida mothers. Materials and Methods: A descriptive exploratory design was applied to explore the factors for preferring the mode of delivery among 250 antenatal mothers, selected by convenient sampling technique. A self-structured dichotomous questionnaire on preference and factors influencing preference for mode of delivery was used. Descriptive and inferential statistical analysis was done using SPSS 20 software. Results: The majority of participants (98.4%) preferred vaginal delivery over elective cesarean section as a mode of delivery. The significant factor influencing preferences was speedy recovery after delivery (89.8%). However, significant factors for preferring the cesarean mode of delivery were the obstetrician's advice and the baby's safety (100%). Conclusion: The majority of women preferred a vaginal mode of delivery; they still undergo cesarean mode of delivery. Considering factors, there is a need to develop a positive attitude toward NVD and actions to create awareness toward a safe mode of delivery by building a mutual trust environment and increasing effective dissemination of correct and neutral delivery option advice.

The exocyst subunit EXOC2 regulates the toxicity of expanded GGGGCC repeats in C9ORF72-ALS/FTD.

GGGGCC (G4C2) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How this genetic mutation leads to neurodegeneration remains largely unknown. Using CRISPR-Cas9 technology, we deleted EXOC2, which encodes an essential exocyst subunit, in induced pluripotent stem cells (iPSCs) derived from C9ORF72-ALS/FTD patients. These cells are viable owing to the presence of truncated EXOC2, suggesting that exocyst function is partially maintained. Several disease-relevant cellular phenotypes in C9ORF72 iPSC-derived motor neurons are rescued due to, surprisingly, the decreased levels of dipeptide repeat (DPR) proteins and expanded G4C2 repeats-containing RNA. The treatment of fully differentiated C9ORF72 neurons with EXOC2 antisense oligonucleotides also decreases expanded G4C2 repeats-containing RNA and partially rescued disease phenotypes. These results indicate that EXOC2 directly or indirectly regulates the level of G4C2 repeats-containing RNA, making it a potential therapeutic target in C9ORF72-ALS/FTD.

The association between anti-smoking legislation and prevalence of acute respiratory illnesses in Indian children.

Objective: Exposure to tobacco smoke causes numerous health problems in children, and create burden on the population in terms of economy, morbidity and mortality. In order to protect the child from exposure to tobacco smoke in the outdoor environment, sufficient legislative enactments are available in Indian legislation. The objective of the present study is to investigate the fact that in absence of any specific laws stating about protection of children from exposure to tobacco smoke in indoor environment, whether outdoor related legislations are sufficient to protect children from exposureand to explore the scope for enforcement of both state and central laws in improving health of children in India. Study design: The study considered cross-sectional survey data of Demographic and Health Survey Data on India, National Family and Health Survey fourth round (NFHS-4) for the year 2015-16 on Indian children (below age of four). Methods: Both bivariate and multivariate logistic regression models were used to assess the impact of anti-smoking laws on the prevalence of acute respiratory infection (ARI) based on the place of residence, indoor tobacco smoke exposure and age of the child. Results: The results have shown an inclination of ARI among children in association with states having single law, rural area resident, exposure to indoor tobacco smoke and age of the child, both as independent or in combination are quite conspicuous, and are found to be underestimated. The logistic regression also revealed the influence of these factors both as independent and even in interaction with other. Conclusions: Legislative intervention through both at central (or national)and state levels through anti-smoking laws will decrease the indoor tobacco smoke exposure as a result ARI prevalence will also decrease among children in India.

Locked down-locked in: experiences of families of young children with autism spectrum disorders in Delhi, India.

Introduction: The onset of the COVID-19 pandemic and subsequent lockdowns in March 2020 disrupted the lives of families across India. The lockdown related restrictions brought forth a multitude of challenges including loss of employment, social isolation, school closures and financial burdens. Specifically, it also resulted in the restriction of health-care services for children with neurodevelopmental disabilities. Methods: This qualitative study was conducted as a part of a larger trial in India to understand the experiences of families of young children with autism during the pandemic. In-depth interviews were carried out with 14 caregivers residing in New Delhi, India. Results: Our findings identified pandemic and lockdown's universal impacts on family life and financial stability stemming from job loss, business closure, and salary deductions, affecting quality of life of families. Furthermore, COVID-19 pandemic's impact on autistic children was evident through limited access to essential services and financial challenges related service interruptions even after resumption of services. The lockdown's novelty also affected children's behavior, with both challenging behavioral changes and positive impacts. Primary caregivers, predominantly mothers, assumed additional responsibilities in household tasks, schooling, and therapy administration. While some these experiences were universally experienced, a few of these improved outcomes for autistic children. Despite challenges, parents expressed gratitude for their family's safety and well-being during the difficult time. Discussions: These findings inform service provision for vulnerable families and offer implications for designing interventions such as credit schemes for families, guidance and resources for establishing and maintaining routines of children with autism, adopting flexible and adaptable approaches to service delivery, and special provisions for children with autism to be able to maintain their routines outside of home. Furthermore, the study highlights the need for comprehensive support, including educational resources and stress management counselling to empower parents in supporting essential care and routines for their children during such unprecedented times.

Exploring the determinants of workplace mental health in a medical institution in central India: A cross-sectional survey.

Introduction: Mental health at the workplace (WMH) is an important indicator for the optimum functioning of a medical institute. To establish an effective WMH, it is essential to understand the level of awareness, perceptions, and felt needs of students and staff of a medical institute regarding mental health services within the campus. Material and Methods: A cross-sectional web-based survey was conducted in an institution of national importance in Central India using a semistructured questionnaire based on Kobo Toolbox. Felt need for periodic mental health screening within the institutional campus (FN-S) and felt need of having a separate cell for mental healthcare of students and employees (FN-C) were analyzed using univariable and multivariable logistic regression. Results: A total of 526 out of 2190 eligible students and staff completed the survey (response rate 24.1%). About half of the participants were not aware, of whom to contact on campus in case of mental health concerns (MHCs), more than three-fourths were not aware of the rights for seeking treatment, and three-fourths thought that getting diagnosed with an MHC would negatively impact their academic course or work. There was a high felt need for mental health screening services (91.1%), and almost two-thirds felt the need for a separate mental health cell. The FN-S was higher among those from rural areas, those not using social media, those without a preexisting MHC, and those without FN-C. FN-C was higher in those not using social media, those having sleep disturbances, those with unawareness of the rights of a mentally ill person, those without any MHC, and those not having FN-S. Conclusion: Active efforts are needed to roll out a mental health screening policy and separate mental health cells within the medical institute. Future research should focus on a qualitative inquiry into the details of the above findings.

Musculoskeletal pain affecting undergraduate nursing students: A cross sectional study on the prevalence and the associated factors.

BACKGROUND: Musculoskeletal pain conditions (MSP) affect not only professional nurses but nursing students too. Long standing pain conditions affecting young individuals in their productive years can impact their work efficiency and can have economic impacts. Effective interventions to decrease the effect of MSP conditions are essential for a healthy professional nursing force which form the backbone of the healthcare system. PURPOSE: We conducted this study with an aim to estimate the prevalence and patterns of MSP conditions in undergraduate nursing students. Additionally, we attempted to evaluate the associated factors and identify the predictors of MSP conditions in them. METHODS: This cross-sectional study was conducted using a web-based electronic questionnaire on nursing students at a tertiary level teaching hospital. The questionnaire prepared on Kobo Toolbox was circulated among the students of each class by their class representative using WhatsApp and e-mail. Two reminders were sent at 24-hour intervals. The data were analysed to identify the prevalence of MSP and evaluate the probable associated factors. RESULTS: One hundred and seventy-nine out of 255 (70.2 %) participants responded and 173 consented for participation. Around 53.2 % participants had suffered from MSP in the past year. A total of 43.9 % of the participants had previously suffered from musculoskeletal pain even earlier than the past one-year in question. Those in their 2nd academic year had higher odds of suffering from MSP. Factors related to self-study after the formal teachings at the school/ college of nursing like the place, duration, and posture, and the pattern of usage of electronic devices like smartphones and laptop computers had no significant association with the MSP conditions. Lack of physical exercise, attending clinical placements, and the factors related to such placements like duration and frequency of placements, and the duration of breaks during any placement were noted to have an influence on MSP. CONCLUSION: More than 50 % students reported to be affected by MSP over a year. Association with factors like inadequate physical activity, and strenuous clinical placements identified in this study indicate that modifications in the nursing curriculum are required. Encouraging physical activity on one hand, while minimising exhaustive, and taxing clinical placements might be the way forward for improving the musculoskeletal health of aspiring nurses.

Alarming Trend in Under-Five Indian Children's Exposure to Indoor Tobacco Smoke.

BACKGROUND AND AIM: Children who are exposed to tobacco smoke (ETS) are at risk for a variety of health issues. There are enough legislative provisions in Indian law to safeguard children from ETS in outdoor settings, but no such specific rules exist to shield them from exposure indoors. This study aimed to examine the trend in under-five children's exposure to indoor tobacco smoke over the course of a decade (from 2005 to 2016) in India. MATERIALS AND METHODS: Data from the National Family and Health Survey (NFHS) for the years 2005-2006 (NFHS-3) and 2015-2016 (NFHS-4) on under-five children have been taken into consideration in cross-sectional analyses of the Demographic and Health Survey on India. Based on different sociodemographic factors, the propensity of indoor ETS among Indian children has been estimated and compared using both bivariate and multivariate logistic regression models. RESULTS: The prevalence of indoor ETS among Indian children under the age of five has greatly risen over the past decade, rising from 4.12% to 52.70%. According to the findings, there has been a noticeable increase in every group of kids, regardless of their age, place of residence, geographic location, socioeconomic status, and literacy level of their mothers. CONCLUSION: In India, the incidence of indoor ETS among children under five has risen by 13 times in the last 10 years, endangering the country. As a result, the Indian government must prepare to take legislative action to safeguard children by passing laws that forbid smoking inside.

Clinicopathological Challenges in Tumors of the Nasal Cavity and Paranasal Sinuses: Our Experience.

Background and objective Nasal and paranasal lesions are one of the most common otorhinolaryngological presentations encountered in clinical practice. Common presenting symptoms of these lesion range from nasal blockades, facial swellings, pain, nasal discharge, and epistaxis to orbital and ear symptoms. Diagnosis can be tricky as these symptoms are common in inflammatory conditions and tumors. The aim of our study was to observe the epidemiology and clinical pathological findings in patients with nasal and paranasal masses presenting to our institute and discuss the challenges in proper diagnosis and management due to similar presentations, and the role of histopathological examination (HPE) and immunohistochemistry (IHC) in overcoming these challenges. Methods The IPD records of 396 patients were taken up for the study. All the specimens were sent in 10% neutral buffered formalin for examination as biopsy for diagnosis or after surgical excision. After adequate fixation, the biopsy specimen was submitted for routine processing, followed by paraffin embedding, and stained with hematoxylin and eosin (H&E). Special stains like periodic acid-Schiff (PAS) and Ziehl-Neelsen (ZN) stains for acid-fast bacilli (AFB) were used as required. IHC was performed in the required samples. IHC markers were performed on representative paraffin-embedded sections according to the streptavidin-biotin immunoperoxidase technique as needed. The findings were noted, and histology was correlated with clinical presentations and investigations, tabulated, and statistically analyzed using SPSS Statistics (IBM, Armonk, NY). Results Of note, 67.92%% were non-neoplastic lesions whereas 18.18% came out to be benign neoplasms and 13.88% were malignant lesions on HPE. Nasal obstruction was the most common presenting symptom (73.23% of patients) followed by nasal mass (64.14% of cases). Inflammatory sinonasal polyps were the most prominent cases in our study, accounting for 41.16% of all lesions; 18.68% fungal RS (mucormycosis) were seen in our study and 4.54% were cases of juvenile nasopharyngeal angiofibroma (JNA). The majority of benign neoplasms encountered were Schneiderian papilloma or inverted papilloma (06.81%). Eighteen (4.54%) cases of squamous cell carcinomas (SCC) were seen in our study and 2.77% (n=11) cases were of adenoid cystic carcinoma. Of 18 cases of SCC, moderately differentiated SCC carcinoma accounted for 10 cases followed by poorly differentiated SCC (5/18) and nonkeratinizing SCC (3/18). IHC for p40 was performed in all the cases of nonkeratinizing SCC, which showed strong and diffuse nuclear positivity. Conclusion The nasal cavity is the site of the most varied presentation of tumors in the upper respiratory tract. Mass in the nose and paranasal sinus (PNS) form a heterogeneous group of lesions with varied histopathological features. The proximity of the area to the eyes and brain warrants early definitive diagnosis so that the lesion is treated before it can involve important and vital centers. Even though malignant nasal tumors have a very low incidence, they cause a lot of morbidity due to their long course and frequent local recurrences. Nasal tumors tend to become polypoidal. Epithelioid papilloma of the nasal cavity often resembles a nasal polyp. Clinical diagnosis can be challenging due to similar presentations and appearances, and hence histological examination is a vital tool for the timely diagnosis of such patients.

Six-Week Hospital-Based Pulmonary Rehabilitation in Covid Pneumonia ICU Survivors: Experience from a Tertiary Care Center in Central India.

OBJECTIVE: There is very limited data on the usefulness of pulmonary rehabilitation in patients with coronavirus pneumonia who have survived intensive care unit care. The primary aim was to explore the feasibility of conducting a pulmonary rehabilitation program in patients with coronavirus disease-19 pneumonia surviving intensive care. The secondary aim was to study the impact of a hospital-based 6-week pulmonary rehabilitation program on exercise capacity, quality of life, and psychological parameters in these patients. This study was conducted at the Center for Pulmonary Rehabilitation, Department of Pulmonary Medicine of the institute. MATERIAL AND METHODS: A total of 27 patients were enrolled. Among them, 14 patients who completed the desired 12 sessions over 6 weeks constituted the pulmonary rehabilitation group and 13 patients who either did not consent or defaulted within the first 2 weeks were considered as controls. Both groups had assessments at 0 and 6 weeks that included a 6-Minute Walk Test, Incremental Shuttle Walk Test, mMRC Dyspnea Scale, Baseline Dyspnea Index, and Transitional Dyspnea Index, Saint George's Respiratory Questionnaire score, and Depression, Anxiety, Stress Scale-21 score. RESULTS: Significant improvement in dyspnea by mMRC (P = .01) and exercise capacity as measured by 6-Minute Walk Test (P <.001) and Incremental Shuttle Walk Test (P = .025) was seen in the pulmonary rehabilitation group as compared to the control group. There was no significant improvement in quality of life and psychological parameters (Depression, Anxiety, Stress Scale 21 score) after 6 weeks of pulmonary rehabilitation program as measured in our study. CONCLUSION: Pulmonary rehabilitation is feasible and appears promising in coronavirus disease acute respiratory distress syndrome survivors. However, data from other centers and a larger number of patients are required to imbibe conclusive results.

Pilot randomised controlled trial of a remotely delivered online intervention for adolescent mental health problems in India: lessons learned about low acceptability and feasibility during the COVID-19 pandemic.

BACKGROUND: 'POD Adventures' is a gamified problem-solving intervention delivered via smartphone app, and supported by non-specialist counsellors for a target population of secondary school students in India during the COVID-19 pandemic. AIMS: To evaluate the feasibility and acceptability of undertaking a randomised controlled trial of POD Adventures when delivered online with telephone support from counsellors. METHOD: We conducted a parallel, two-arm, individually randomised pilot-controlled trial with 11 secondary schools in Goa, India. Participants received either the POD Adventures intervention delivered over 4 weeks or usual care comprising information about local mental health services and national helplines. Outcomes were assessed at two timepoints: baseline and 6 weeks post-randomisation. RESULTS: Seventy-nine classroom sensitisation sessions reaching a total of 1575 students were conducted. Ninety-two self-initiated study referrals (5.8%) were received, but only 11 participants enrolled in the study. No intervention arm participants completed the intervention. Outcomes at 6 weeks were not available for intervention arm participants (n = 5), and only four control arm participants completed outcomes. No qualitative interviews or participant satisfaction measures were completed because participants could not be reached by the study team. CONCLUSIONS: Despite modifications to address barriers arising from COVID-19 restrictions, online delivery was not feasible in the study context. Low recruitment and missing feasibility and acceptability data make it difficult to draw conclusions about intervention engagement and indicative clinical outcomes. Prior findings showing high uptake, adherence and engagement with POD Adventures when delivered in a school-based context suggest that an online study and delivery posed the biggest barriers to study participation and engagement.

Impact of an Anti-Microbial Stewardship Program on Targeted Antimicrobial Therapy in a Tertiary Care Health Care Institute in Central India.

Introduction Antimicrobial resistance (AMR) has become a global pandemic. In order to identify this menace, World Health Organisation (WHO) has developed the Global Action Plan on AMR (GAP AMR). Antimicrobial stewardship programs (AMSP) have been identified as a decisive tool for combating AMR. One of the most efficient measures of these programs has been the implementation of point prevalence surveys (PPS) of antibiotic usage and subsequent audit feedback. The present study was undertaken to identify the impact of AMSP on curtailing of empirical usage of antibiotics and the augmentation of targeted therapy.  Methods It is an observational, cross-sectional study comprising 1396 patients. The microbiology culture details and anti-microbial-sensitivity results were recorded. Antibiotic prescriptions were recorded in each patient during their hospital stay. Result Out of 1396 patients treated over four quarters (Q1-Q4), 711 (50.9%) patients were on antibiotics, and among them, only 415 patients were subjected to any microbiological cultures with an overall bacterial culture rate (BCR) of 58.3%, and 296 patients (41.6%) were treated with antibiotics empirically without sending any samples for bacterial culture. There was a statistically significant rise in BCR from 47.3% in the first quarter to 77.6% in the fourth quarter. Sending specimens for blood culture increased significantly from 29.2% in Q1 to 37.6% in Q4. After receiving culture reports, 72.3% of cases continued with the same antibiotic, the antibiotic was changed in 19.9% of cases, and the antibiotic was stopped in 7.8% of cases. Conclusion There was a strong positive impact of AMSP in curtailment of empirical usage of antibiotics and augmenting targeted therapy as evidenced by the significant rise in BCR over Q1-Q4 PPS as well as a significant rise in ordering for blood culture over the same time period.

PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling.

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.

The uncharacterized protein FAM47E interacts with PRMT5 and regulates its functions.

Protein arginine methyltransferase 5 (PRMT5) symmetrically dimethylates arginine residues in various proteins affecting diverse cellular processes such as transcriptional regulation, splicing, DNA repair, differentiation, and cell cycle. Elevated levels of PRMT5 are observed in several types of cancers and are associated with poor clinical outcomes, making PRMT5 an important diagnostic marker and/or therapeutic target for cancers. Here, using yeast two-hybrid screening, followed by immunoprecipitation and pull-down assays, we identify a previously uncharacterized protein, FAM47E, as an interaction partner of PRMT5. We report that FAM47E regulates steady-state levels of PRMT5 by affecting its stability through inhibition of its proteasomal degradation. Importantly, FAM47E enhances the chromatin association and histone methylation activity of PRMT5. The PRMT5-FAM47E interaction affects the regulation of PRMT5 target genes expression and colony-forming capacity of the cells. Taken together, we identify FAM47E as a protein regulator of PRMT5, which promotes the functions of this versatile enzyme. These findings imply that disruption of PRMT5-FAM47E interaction by small molecules might be an alternative strategy to attenuate the oncogenic function(s) of PRMT5.

SET7/9 interacts and methylates the ribosomal protein, eL42 and regulates protein synthesis.

Methylation of proteins is emerging to be an important regulator of protein function. SET7/9, a protein lysine methyltransferase, catalyses methylation of several proteins involved in diverse biological processes. SET7/9-mediated methylation often regulates the stability, sub-cellular localization and protein-protein interactions of its substrate proteins. Here, we aimed to identify novel biological processes regulated by SET7/9 by identifying new interaction partners. For this we used yeast two-hybrid screening and identified the large subunit ribosomal protein, eL42 as a potential interactor of SET7/9. We confirmed the SET7/9-eL42 interaction by co-immunoprecipitation and GST pulldown studies. The N-terminal MORN domain of SET7/9 is essential for its interaction with eL42. Importantly, we identified that SET7/9 methylates eL42 at three different lysines - Lys53, Lys80 and Lys100 through site-directed mutagenesis. By puromycin incorporation assay, we find that SET7/9-mediated methylation of eL42 affects global translation. This study identifies a new role of the functionally versatile SET7/9 lysine methyltransferase in the regulation of global protein synthesis.