Similar Datasets
Project description:The FASTK family proteins are emerging key post-transcriptional regulators in mitochondrial gene expression. In attempts to uncover their molecular functions, we carried out BioID experiments to identify proteins interacting with FASTKD4 and FASTKD5. Our data suggest that both proteins have similar protein interactome profiles, highlighting their roles in mitochondrial RNA processing.
2021-11-02 | PXD020993 | Pride
Project description:The FASTK family proteins are master regulators in mitochondrial RNA processing
| PRJNA658336 | ENA
Project description:Canonical RNA processing in mammalian mitochondria necessitates that tRNAs are recognised by nucleases to release flanking transcripts. However, not all mitochondrial transcripts are punctuated by tRNAs, and the mechanism and factors involved in their processing has remained unsolved. Here, we demonstrate that phosphatase activity of the carbon catabolite repressor 4 domain containing family member ANGEL2 is required for the hydrolysis of 3′ phosphates, resulting from non-canonical processing. Interaction studies in Drosophila further identify that members of the FAST kinase domain containing protein family are involved in the formation of these 3′ phosphates. Our results therefore resolve the mechanism of RNA processing in metazoan mitochondria, by defining the outstanding non-canonical processing mechanism.
2022-09-04 | GSE189750 | GEO
Project description:Sphingolipids comprise a diverse family of lipids that perform multiple functions in both structure of cellular membranes and intra- and inter-cellular signaling. The diversity of this family is generated by an array of enzymes that produce individual classes and molecular species of family members and enzymes which catabolize those lipids for recycling pathways. However, all of these lipids begin their lives with a single step, the condensation of an amino acid, almost always serine, and a fatty acyl-CoA, almost always the 16-carbon, saturated fatty acid, palmitate. The enzyme complex that accomplishes this condensation is serine palmitoyltransferase (SPT), a membrane-bound component of the endoplasmic reticulum. This places SPT in the unique position of regulating the production of the entire sphingolipid pool. Understanding how SPT activity is regulated is currently a central focus in the field of sphingolipid biology. In this review we examine the regulation of SPT activity by a set of small, membrane-bound proteins of the endoplasmic reticulum, the Orms (in yeast) and ORMDLs (in vertebrates). We discuss what is known about how these proteins act as homeostatic regulators by monitoring cellular levels of sphingolipid, but also how the Orms/ORMDLs regulate SPT in response to other stimuli. Finally, we discuss the intriguing connection between one of the mammalian ORMDL isoforms, ORMDL3, and the pervasive pulmonary disease, asthma, in humans.
| S-EPMC6251742 | biostudies-literature
Project description:Transcription of the human mitochondrial genome and correct processing of the two long polycistronic transcripts are crucial for oxidative phosphorylation. According to the tRNA punctuation model, nucleolytic processing of these large precursor transcripts occurs mainly through the excision of the tRNAs that flank most rRNAs and mRNAs. However, some mRNAs are not punctuated by tRNAs, and it remains largely unknown how these non-canonical junctions are resolved. The FASTK family proteins are emerging as key players in non-canonical RNA processing. Here, we have generated human cell lines carrying single or combined knockouts of several FASTK family members to investigate their roles in non-canonical RNA processing. The most striking phenotypes were obtained with loss of FASTKD4 and FASTKD5 and with their combined double knockout. Comprehensive mitochondrial transcriptome analyses of these cell lines revealed a defect in processing at several canonical and non-canonical RNA junctions, accompanied by an increase in specific antisense transcripts. Loss of FASTKD5 led to the most severe phenotype with marked defects in mitochondrial translation of key components of the electron transport chain complexes and in oxidative phosphorylation. We reveal that the FASTK protein family members are crucial regulators of non-canonical junction and non-coding mitochondrial RNA processing.
| S-EPMC8601606 | biostudies-literature
Project description:The FASTK family proteins have recently emerged as key post-transcriptional regulators of mitochondrial gene expression. FASTK, the founding member and its homologs FASTKD1-5 are architecturally related RNA-binding proteins, each having a different function in the regulation of mitochondrial RNA biology, from mRNA processing and maturation to ribosome assembly and translation. In this review, we outline the structure, evolution and function of these FASTK proteins and discuss the individual role that each has in mitochondrial RNA biology. In addition, we highlight the aspects of FASTK research that still require more attention.
| S-EPMC5737537 | biostudies-literature
Project description:The formation of mammalian synapses entails the precise alignment of presynaptic release sites with postsynaptic receptors but how nascent cell-cell contacts translate into assembly of presynaptic specializations remains unclear. Guided by pioneering work in invertebrates, we hypothesized that in mammalian synapses, liprin-α proteins directly link trans-synaptic initial contacts to downstream steps. Here we show that, in human neurons lacking all four liprin-α isoforms, nascent synaptic contacts are formed but recruitment of active zone components and accumulation of synaptic vesicles is blocked, resulting in 'empty' boutons and loss of synaptic transmission. Interactions with presynaptic cell adhesion molecules of either the LAR-RPTP family or neurexins via CASK are required to localize liprin-α to nascent synaptic sites. Liprin-α subsequently recruits presynaptic components via a direct interaction with ELKS proteins. Thus, assembly of human presynaptic terminals is governed by a hierarchical sequence of events in which the recruitment of liprin-α proteins by presynaptic cell adhesion molecules is a critical initial step.
| S-EPMC11001580 | biostudies-literature
Project description:Canonical RNA processing in mammalian mitochondria is defined by tRNAs acting as recognition sites for nucleases to release flanking transcripts. The relevant factors, their structures, and mechanism are well described, but not all mitochondrial transcripts are punctuated by tRNAs, and their mode of processing has remained unsolved. Using Drosophila and mouse models, we demonstrate that non-canonical processing results in the formation of 3′ phosphates, and that phosphatase activity by the carbon catabolite repressor 4 domain-containing family member ANGEL2 is required for their hydrolysis. Furthermore, our data suggest that members of the FAST kinase domain-containing protein family are responsible for these 3′ phosphates. Our results therefore resolve the mechanism of non-canonical RNA processing in metazoan mitochondria, by defining the role of ANGEL2.
2022-09-01 | PXD033394 | Pride
Project description:Angel2 phosphatase activity is required for non-canonical mitochondrial RNA processing in metazoa
| PRJNA784409 | ENA
Project description:Abiotic stresses such as drought and salinity are major environmental factors that limit crop yields. Unraveling the molecular mechanisms underlying abiotic stress resistance is crucial for improving crop performance and increasing productivity under adverse environmental conditions. Zinc finger proteins, comprising one of the largest transcription factor families, are known for their finger-like structure and their ability to bind Zn2+. Zinc finger proteins are categorized into nine subfamilies based on their conserved Cys and His motifs, including the Cys2/His2-type (C2H2), C3H, C3HC4, C2HC5, C4HC3, C2HC, C4, C6, and C8 subfamilies. Over the past two decades, much progress has been made in understanding the roles of C2H2 zinc finger proteins in plant growth, development, and stress signal transduction. In this review, we focus on recent progress in elucidating the structures, functions, and classifications of plant C2H2 zinc finger proteins and their roles in abiotic stress responses.
| S-EPMC7044346 | biostudies-literature