The histone acylation reader ENL/AF9 regulates aging in Drosophila melanogaster.

Histone acylation plays a pivotal role in modulating gene expression, ensuring proper neurogenesis and responsiveness to various signals. Recently, the evolutionary conserved YAF9, ENL, AF9, TAF41, SAS5 (YEATS) domain found in four human paralogs, has emerged as a new class of histone acylation reader with a preference for the bulkier crotonyl group lysine over acetylation. Despite advancements, the role of either histone crotonylation or its readers in neurons remains unclear.

Human Leukocyte Antigen Markers for Distinguishing Pustular Psoriasis and Adult-Onset Immunodeficiency with Pustular Reaction.

Pustular skin diseases, with pustular psoriasis (PP) being the prototype, are immune-mediated diseases characterized by the presence of multiple pustules, resulting from neutrophil accumulation in the layer of epidermis. Sterile skin pustular eruption, like PP, is also observed in 20-30% of patients with adult-onset immunodeficiency syndrome (AOID) and anti-interferon γ autoantibodies (IFN-γ), leading to challenges in classification and diagnosis. While the mechanism underlying this similar phenotype remains unknown, genetic factors in relation to the immune system are suspected of playing an important role.

Combinatorial Gene Expression Profiling of Serum , , and lncRNAs to Differentiate Hepatocellular Carcinoma from Liver Diseases: A Systematic Review and Meta-Analysis.

Hepatocellular carcinoma (HCC) presents a significant global health challenge due to limited early detection methods, primarily relying on conventional approaches like imaging and alpha-fetoprotein (AFP). Although non-coding RNAs (ncRNAs) show promise as potential biomarkers in HCC, their true utility remains uncertain. We conducted a comprehensive review of 76 articles, analyzing 88 circulating lncRNAs in 6426 HCC patients.

FAME4-associating YEATS2 knockdown impairs dopaminergic synaptic integrity and leads to seizure-like behaviours in Drosophila melanogaster.

Familial adult myoclonus epilepsy (FAME) is a neurological disorder caused by a TTTTA/TTTCA intronic repeat expansion. FAME4 is one of the six types of FAME that results from the repeat expansion in the first intron of the gene YEATS2. Although the RNA toxicity is believed to be the primary mechanism underlying FAME, the role of genes where repeat expansions reside is still unclear, particularly in the case of YEATS2 in neurons.

A Novel Drosophila-based Drug Repurposing Platform Identified Fingolimod As a Potential Therapeutic for TDP-43 Proteinopathy.

Pathogenic changes to TAR DNA-binding protein 43 (TDP-43) leading to alteration of its homeostasis are a common feature shared by several progressive neurodegenerative diseases for which there is no effective therapy. Here, we developed Drosophila lines expressing either wild type TDP-43 (WT) or that carrying an Amyotrophic Lateral Sclerosis /Frontotemporal Lobar Degeneration-associating G384C mutation that recapitulate several aspects of the TDP-43 pathology. To identify potential therapeutics for TDP-43-related diseases, we implemented a drug repurposing strategy that involved three consecutive steps.

Multifaceted roles of YEATS domain-containing proteins and novel links to neurological diseases.

The so-called Yaf9, ENL, AF9, Taf14, and Sas5 (YEATS) domain-containing proteins, hereafter referred to as YD proteins, take control over the transcription by multiple steps of regulation either involving epigenetic remodelling of chromatin or guiding the processivity of RNA polymerase II to facilitate elongation-coupled mRNA 3' processing. Interestingly, an increasing amount of evidence suggest a wider repertoire of YD protein's functions spanning from non-coding RNA regulation, RNA-binding proteins networking, post-translational regulation of a few signalling transduction proteins and the spindle pole formation. However, such a large set of non-canonical roles is still poorly characterized.

In search of TP53 mutational hot spots for Li-Fraumeni syndrome in Asian populations.

Objective: Germline mutations of the TP53 tumour suppressor gene are the only known cause of the hereditary autosomal disorder called Li-Fraumeni syndrome (LFS). However, little information is available about TP53 pathogenic variants in Asian LFS patients, making it difficult to provide precise genetic counselling with regard to long-term cancer risk. We conducted a systematic review to gather relevant case-control studies exploring the association between TP53 polymorphisms and the incidence of cancer belonging to the LFS spectrum in Asian populations.

Circulating Long Non-Coding RNAs as Novel Potential Biomarkers for Osteogenic Sarcoma.

Circulating cell-free nucleic acids recently became attractive targets to develop non-invasive diagnostic tools for cancer detection. Along with DNA and mRNAs, transcripts lacking coding potential (non-coding RNAs, ncRNAs) directly involved in the process of tumor pathogenesis have been recently detected in liquid biopsies. Interestingly, circulating ncRNAs exhibit specific expression patterns associated with cancer and suggest their role as novel biomarkers.

Long noncoding RNA-dependent methylation of nonhistone proteins.

In the last decade, an intriguing new paradigm of regulation has emerged in which some transcripts longer than 200 nucleotides and no coding potential, long noncoding RNA (lncRNAs), exhibit the capability to control posttranslational modifications of nonhistone proteins in both invertebrates and vertebrates. The extent of such a regulation is still largely unknown. We performed a systematic review to identify and evaluate the potential impact of lncRNA-dependent methylation of nonhistone proteins.

Ubiquilin Networking in Cancers.

Ubiquilins or UBQLNs, members of the ubiquitin-like and ubiquitin-associated domain (UBL-UBA) protein family, serve as adaptors to coordinate the degradation of specific substrates via both proteasome and autophagy pathways. The UBQLN substrates reveal great diversity and impact a wide range of cellular functions. For decades, researchers have been attempting to uncover a puzzle and understand the role of UBQLNs in human cancers, particularly in the modulation of oncogene's stability and nucleotide excision repair.

The lncRNA regulates arginine dimethylation of human FUS to cause its proteasomal degradation in .

Long non-coding RNAs (lncRNAs) have structural and regulatory effects on RNA-binding proteins (RBPs). However, the mechanisms by which lncRNAs regulate the neurodegenerative-causative RBP like FUS protein remain poorly understood. Here, we show that knockdown of the lncRNA causes a shift in the methylation status of human FUS from mono- (MMA) to di-methylated (DMA) arginine via upregulation of the arginine methyltransferase 5 (PRMT5, known as ART5 in flies).

Non-Proteasomal UbL-UbA Family of Proteins in Neurodegeneration.

Ubiquitin-like/ubiquitin-associated proteins (UbL-UbA) are a well-studied family of non-proteasomal ubiquitin receptors that are evolutionarily conserved across species. Members of this non-homogenous family facilitate and support proteasomal activity by promoting different effects on proteostasis but exhibit diverse extra-proteasomal activities. Dysfunctional UbL-UbA proteins render cells, particularly neurons, more susceptible to stressors or aging and may cause earlier neurodegeneration.

Genetic screening of the genes interacting with Drosophila FIG4 identified a novel link between CMT-causing gene and long noncoding RNAs.

Neuron-specific knockdown of the dFIG4 gene, a Drosophila homologue of human FIG4 and one of the causative genes for Charcot-Marie-Tooth disease (CMT), reduces the locomotive abilities of adult flies, as well as causing defects at neuromuscular junctions, such as reduced synaptic branch length in presynaptic terminals of the motor neurons in third instar larvae. Eye imaginal disc-specific knockdown of dFIG4 induces abnormal morphology of the adult compound eye, the rough eye phenotype. In this study, we carried out modifier screening of the dFIG4 knockdown-induced rough eye phenotype using a set of chromosomal deficiency lines on the second chromosome.

Drosophila as a Model to Gain Insight into the Role of lncRNAs in Neurological Disorders.

It is now clear that the majority of transcription in humans results in the production of long non-protein-coding RNAs (lncRNAs) with a variable length spanning from 200 bp up to several kilobases. To date, we have a limited understanding of the lncRNA function, but a huge number of evidences have suggested that lncRNAs represent an outstanding asset for cells. In particular, temporal and spatial expression of lncRNAs appears to be important for proper neurological functioning.

Depletion of Ubiquilin induces an augmentation in soluble ubiquitinated Drosophila TDP-43 to drive neurotoxicity in the fly.

The proteostasis machinery has critical functions in metabolically active cells such as neurons. Ubiquilins (UBQLNs) may decide the fate of proteins, with its ability to bind and deliver ubiquitinated misfolded or no longer functionally required proteins to the ubiquitin-proteasome system (UPS) and/or autophagy. Missense mutations in UBQLN2 have been linked to X-linked dominant amyotrophic lateral sclerosis with frontotemporal dementia (ALS-FTD).

Loss of ISWI Function in Drosophila Nuclear Bodies Drives Cytoplasmic Redistribution of Drosophila TDP-43.

Over the past decade, evidence has identified a link between protein aggregation, RNA biology, and a subset of degenerative diseases. An important feature of these disorders is the cytoplasmic or nuclear aggregation of RNA-binding proteins (RBPs). Redistribution of RBPs, such as the human TAR DNA-binding 43 protein (TDP-43) from the nucleus to cytoplasmic inclusions is a pathological feature of several diseases.

A new Drosophila model of Ubiquilin knockdown shows the effect of impaired proteostasis on locomotive and learning abilities.

Ubiquilin (UBQLN) plays a crucial role in cellular proteostasis through its involvement in the ubiquitin proteasome system and autophagy. Mutations in the UBQLN2 gene have been implicated in amyotrophic lateral sclerosis (ALS) and ALS with frontotemporal lobar dementia (ALS/FTLD). Previous studies reported a key role for UBQLN in Alzheimer's disease (AD); however, the mechanistic involvement of UBQLN in other neurodegenerative diseases remains unclear.

FUS toxicity is rescued by the modulation of lncRNA hsrω expression in Drosophila melanogaster.

FUS is an aggregation-prone hnRNP involved in transcriptional and post-transcriptional regulation that aberrantly forms immunoreactive inclusion bodies in a range of neurological diseases classified as FUS-proteinopathies. Although FUS has been extensively examined, the underlying molecular mechanisms of these diseases have not yet been elucidated in detail. We previously reported that RNAi of the lncRNA hsrω altered the expression and sub-cellular localization of Drosophila FUS in the central nervous system of the fly.

RNAi of arcRNA hsrω affects sub-cellular localization of Drosophila FUS to drive neurodiseases.

Defective RNA metabolism is common pathogenic mechanisms involved in neurological disorders. Indeed, a conspicuous feature of some neurodegenerative diseases is the loss of nuclear activities of RNA-binding proteins (RBPs) like Fused in sarcoma (FUS) and eventually, their accumulation in cytoplasmic proteinaceous inclusions. Long non-coding RNAs (lncRNAs) are emerging as important regulators of tissue physiology and disease processes, including neurological disorders.

ISWI ATP-dependent remodeling of nucleoplasmic ω-speckles in the brain of Drosophila melanogaster.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) belong to the RNA-binding proteins family. They are involved in processing heterogeneous nuclear RNAs (hnRNAs) into mature mRNAs. These proteins participate in every step of mRNA cycle, such as mRNA export, localization, translation, stability and alternative splicing.

Nuclear and Cytoplasmic Soluble Proteins Extraction from a Small Quantity of Drosophila's Whole Larvae and Tissues.

The identification and study of protein's function in several model organisms is carried out using both nuclear and cytoplasmic extracts. For a long time, Drosophila's embryos have represented the main source for protein extractions, although in the last year, the importance of collecting proteins extracts also from larval tissues has also been understood. Here we report a very simple protocol, improved by a previously developed method, to produce in a single extraction both highly stable nuclear and cytoplasmic protein extracts from a small quantity of whole Drosophila's larvae or tissues, suitable for biochemical analyses like co-immunoprecipitation.

Emerging roles for hnRNPs in post-transcriptional regulation: what can we learn from flies?

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a highly conserved family of RNA-binding proteins able to associate with nascent RNAs in order to support their localization, maturation and translation. Research over this last decade has remarked the importance of gene regulatory processes at post-transcriptional level, highlighting the emerging roles of hnRNPs in several essential biological events. Indeed, hnRNPs are key factors in regulating gene expression, thus, having a number of roles in many biological pathways.

Differential proteomic analysis of an engineered Streptomyces coelicolor strain reveals metabolic pathways supporting growth on n-hexadecane.

The alkB gene, encoding an alkane monooxygenase in the actinomycete Gordonia sp. SoCg, was expressed in the non-alkane-degrading actinomycete Streptomyces coelicolor M145. The resulting engineered strain, M145-AH, can grow on n-hexadecane as sole carbon source.