Implications of the SRP72 p.R124S mutation on signal recognition particle functions [K562_SRP72]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE222812 | GEO | 2023/05/02
REPOSITORIES: GEO
Similar Datasets
Project description:Implications of the SRP72 p.R124S mutation on signal recognition particle functions [K562_SRP72]
| PRJNA923605 | ENA
Project description:The signal-recognition particle (SRP) is a ubiquitous protein-RNA complex that targets proteins to cellular membranes for insertion or secretion. A key player in SRP-mediated protein targeting is the evolutionarily conserved core consisting of the SRP RNA and the multidomain protein SRP54. Communication between the SRP54 domains is critical for SRP function, where signal sequence binding at the M domain directs receptor binding at the GTPase domain (NG domain). These SRP activities are linked to domain rearrangements, for which the role of SRP RNA is not clear. In free SRP, a direct interaction of the GTPase domain with SRP RNA has been proposed but has never been structurally verified. In this study, we present the crystal structure at 2.5-A resolution of the SRP54-SRP19-SRP RNA complex of Methanococcus jannaschii SRP. The structure reveals an RNA-bound conformation of the SRP54 GTPase domain, in which the domain is spatially well separated from the signal peptide binding site. The association of both the N and G domains with SRP RNA in free SRP provides further structural evidence for the pivotal role of SRP RNA in the regulation of the SRP54 activity.
| S-EPMC1986587 | biostudies-literature
Project description:To investigate the functional significance of STIM1::MXD3, we overexpressed the fusion gene in K562 myeloid leukemia cells and analysed global gene expression changes using RNA-seq.
2023-05-02 | GSE222813 | GEO
Project description:To investigate the functional significance and transcriptional impacts associated with RUNX1::ERG, we overexpressed the fusion gene in K562 myeloid leukemia cells and analysed global gene expression changes using RNA-seq.
2023-05-02 | GSE222811 | GEO
Project description:The signal recognition particle (SRP) is a ribonucleoprotein complex fundamental for co-translational delivery of proteins to their proper membrane localization and secretory pathways. Literature of the past two decades has suggested new roles for individual SRP components, 7SL RNA and proteins SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72, outside the SRP cycle. These noncanonical functions interconnect SRP with a multitude of cellular and molecular pathways, including virus-host interactions, stress response, transcriptional regulation and modulation of apoptosis in autoimmune diseases. Uncovered novel properties of the SRP components present a new perspective for the mammalian SRP as a biological modulator of multiple cellular processes. As a consequence of these findings, SRP components have been correlated with a growing list of diseases, such as cancer progression, myopathies and bone marrow genetic diseases, suggesting a potential for development of SRP-target therapies of each individual component. For the first time, here we present the current knowledge on the SRP noncanonical functions and raise the need of a deeper understanding of the molecular interactions between SRP and accessory cellular components. We examine diseases associated with SRP components and discuss the development and feasibility of therapeutics targeting individual SRP noncanonical functions.
| S-EPMC8185352 | biostudies-literature
Project description:Targeting of proteins to appropriate subcellular compartments is a crucial process in all living cells. Secretory and membrane proteins usually contain an amino-terminal signal peptide, which is recognized by the signal recognition particle (SRP) when nascent polypeptide chains emerge from the ribosome. The SRP-ribosome nascent chain complex is then targeted through its GTP-dependent interaction with SRP receptor to the protein-conducting channel on endoplasmic reticulum membrane in eukaryotes or plasma membrane in bacteria. A universally conserved component of SRP (refs 1, 2), SRP54 or its bacterial homologue, fifty-four homologue (Ffh), binds the signal peptides, which have a highly divergent sequence divisible into a positively charged n-region, an h-region commonly containing 8-20 hydrophobic residues and a polar c-region. No structure has been reported that exemplifies SRP54 binding of any signal sequence. Here we have produced a fusion protein between Sulfolobus solfataricus SRP54 (Ffh) and a signal peptide connected via a flexible linker. This fusion protein oligomerizes in solution through interaction between the SRP54 and signal peptide moieties belonging to different chains, and it is functional, as demonstrated by its ability to bind SRP RNA and SRP receptor FtsY. We present the crystal structure at 3.5 A resolution of an SRP54-signal peptide complex in the dimer, which reveals how a signal sequence is recognized by SRP54.
| S-EPMC2897128 | biostudies-literature
Project description:The signal recognition particle database (SRPDB) is maintained at the University of Texas Health Science Center at Tyler, Texas, and organizes SRP-related information about SRP RNA, SRP proteins and the SRP receptor. SRPDB is accessible on the WWW at the URL http://psyche.uthct.edu/dbs/SRPDB/SRPDB.++ +html. A mirror site of the SRPDB is located in Europe at the University of Göteborg, Sweden (http://www.medkem. gu.se/dbs/SRPDB/SRPDB.html ). This release of SRPDB adds 10 new SRP RNA sequences (a total of 117 SRP RNAs), four protein SRP19 sequences (a total of 15), seven new SRP54 (ffh) sequences (a total of 52), and eight sequences of the SRP receptor alpha subunit (FtsY) (total of 36). Sequences are arranged in alphabetical and phylogenetic order and alignments are provided which highlight base paired and conserved regions. SPRDB also provides motifs to find new sequences, a brief introduction to SRP function in protein secretion, numerous SRP RNA secondary structure diagrams, 3-D SRP RNA models, and recently obtained crystal structure PDB coordinates of the human SRP54m domain.
| S-EPMC102405 | biostudies-literature
Project description:The signal recognition particle (SRP) is a ribonucleoprotein complex with dual functions. It co-translationally targets proteins with a signal sequence to the endoplasmic reticulum (ER) and protects their mRNA from degradation. If SRP is depleted or cannot recognize the signal sequence, then the Regulation of Aberrant Protein Production (RAPP) is activated, which results in the loss of secretory protein mRNA. If SRP recognizes the substrates but is unable to target them to ER, they may mislocalize or degrade. All these events lead to dramatic consequence for protein biogenesis, activating protein quality control pathways, and creating pressure on cell physiology, and might lead to the pathogenesis of disease. Indeed, SRP dysfunction is involved in many different human diseases, including: congenital neutropenia; idiopathic inflammatory myopathy; viral, protozoal, and prion infections; and cancer. In this work, we analyze diseases caused by SRP failure and discuss their possible molecular mechanisms.
| S-EPMC9214365 | biostudies-literature
Project description:The signal recognition particle (SRP) is a ribonucleoprotein composed of an Alu domain and an S domain. The S domain contains unique sequence SRP RNA and four SRP proteins: SRP19, SRP54, SRP68, and SRP72. SRP interacts with ribosomes to bring translating membrane and secreted proteins to the endoplasmic reticulum (ER) for proper processing. Additionally, SRP RNA is a member of a family of small nonribosomal RNAs found recently in the nucleolus, suggesting that the nucleolus is more plurifunctional than previously realized. It was therefore of interest to determine whether other SRP components localize to this intranuclear site. In transfected rat fibroblasts, green fluorescent protein fusions of SRP19, SRP68, and SRP72 localized to the nucleolus, as well as to the cytoplasm, as expected. SRP68 also accumulated in the ER, consistent with its affinity for the ER-bound SRP receptor. SRP54 was detected in the cytoplasm as a green fluorescent protein fusion and in immunofluorescence studies, but was not detected in the nucleolus. In situ hybridization experiments also revealed endogenous SRP RNA in the nucleolus. These results demonstrate that SRP RNA and three SRP proteins visit the nucleolus, suggesting that partial SRP assembly, or another unidentified activity of the SRP components, occurs at the nucleolus. SRP54 apparently interacts with nascent SRP beyond the nucleolus, consistent with in vitro reconstitution experiments showing that SRP19 must bind to SRP RNA before SRP54 binds. Our findings support the notion that the nucleolus is the site of assembly and/or interaction between the family of ribonucleoproteins involved in protein synthesis, in addition to ribosomes themselves.
| S-EPMC26615 | biostudies-literature
Project description:We describe a method for prediction of genes that encode the RNA component of the signal recognition particle (SRP). A heuristic search for the strongly conserved helix 8 motif of SRP RNA is combined with covariance models that are based on previously known SRP RNA sequences. By screening available genomic sequences we have identified a large number of novel SRP RNA genes and we can account for at least one gene in every genome that has been completely sequenced. Novel bacterial RNAs include that of Thermotoga maritima, which, unlike all other non-gram-positive eubacteria, is predicted to have an Alu domain. We have also found the RNAs of Lactococcus lactis and Staphylococcus to have an unusual UGAC tetraloop in helix 8 instead of the normal GNRA sequence. An investigation of yeast RNAs reveals conserved sequence elements of the Alu domain that aid in the analysis of these RNAs. Analysis of the human genome reveals only two likely genes, both on chromosome 14. Our method for SRP RNA gene prediction is the first convenient tool for this task and should be useful in genome annotation.
| S-EPMC137091 | biostudies-literature