Similar Datasets
Project description:Coordination of gene regulatory networks is necessary for proper execution of cellular programs throughout development. RNA interference (RNAi) is an essential regulatory mechanism in all metazoans. Proper RNAi-mediated gene regulation requires coordination of several RNAi branches to ensure homeostasis. For example, in Caenorhabditis elegans, the Argonautes, ALG-3 and ALG-4, are expressed specifically during spermatogenesis (L4 stage) and bind small interfering RNAs (siRNAs) complementary to sperm-enriched genes. We find that alg-3 and alg-4 are regulated by siRNAs. Our work shows that gene switches are operated via these siRNAs to regulate the Argonautes' expression in a temporal manner. This RNAi-to-RNAi regulatory cascade is essential for coordinating ALG-3/4 pathway function, particularly during heat stress, to provide thermotolerant sperm-based fertility. This work provides insight into one regulatory motif used to maintain RNAi homeostasis, across developmental stages, despite environmental stressors. As RNAi pathways are evolutionarily conserved, other species likely use similar regulatory architectures to maintain RNAi homeostasis.
| S-EPMC11381353 | biostudies-literature
Project description:Coordination of gene regulatory networks is necessary for proper execution of cellular programs throughout development. RNA interference (RNAi) is an essential regulatory mechanism in all metazoans. Proper RNAi-mediated gene regulation requires coordination of several RNAi branches to ensure homeostasis. For example, in C. elegans, the Argonautes, ALG-3 and ALG-4, are expressed specifically during spermatogenesis (L4 stage) and bind small interfering RNAs (siRNAs) complementary to sperm-enriched genes. We find that alg-3 and alg-4 are regulated by siRNAs. Our work shows that gene switches are operated via these siRNAs to regulate the Argonautes’ expression in a temporal manner. This RNAi-to-RNAi regulatory cascade is essential for coordinating ALG-3/4 pathway function, particularly during heat stress, to provide thermotolerant sperm-based fertility. This work provides insight into one regulatory motif used to maintain RNAi homeostasis, across developmental stages, despite environmental stressors. As RNAi pathways are evolutionarily conserved, other species likely use similar regulatory architectures to maintain RNAi homeostasis.
2024-06-25 | GSE226891 | GEO
Project description:Small RNA-mediated genetic switches coordinate ALG-3/4 small RNA pathway function
| PRJNA941966 | ENA
Project description:Small RNA-mediated genetic switches coordinate ALG-3/4 small RNA pathway function
| PRJNA941964 | ENA
Project description:The GAIT (gamma-interferon-activated inhibitor of translation) complex or miR-297-RISC (RNA-induced silencing complex), together with hnRNP L or hnRNP L-bearing complex, operates an RNA switch in myeloid cells that regulates stress-dependent expression of vascular endothelial growth factor-A (VEGFA). Here, we have shown that hnRNP L directs multiple hypoxia-inducible RNA switches simultaneously and regulates expression of these oncogenic genes in addition to VEGFA. Bioinformatic and polysome profiling-microarray screens have identified DNM1L (Dynamin 1-like) and PHF21A (PHD finger protein 21A) mRNAs as regulated at the translational level by GAIT-dependent, hnRNP L-directed RNA switches. We have also uncovered CDK6 (Cyclin dependent kinase 6), MKLN1 (Muskelin 1) and EIF5 (Eukaryotic initiation factor 5) as novel miR-297-dependent, hnRNP L-directed RNA switch transcripts. Src Kinase is required for the phosphorylation of hnRNP L and activation of the RNA switch pathway. Knockdown of hnRNP L sensitizes the human U937 monocytic cells under hypoxia stress but not in normoxia via inducing cell apoptosis partially due to the reduced translation of hnRNP L target mRNAs. Collectively, our findings suggest that commonly controlled genes by the hnRNP L-directed RNA switches form a translational regulon that promotes hypoxia resistance and cell survival.
| S-EPMC6646067 | biostudies-literature
Project description:Germ granules are biomolecular condensates present in most animal germ cells. One function of germ granules is to help maintain germ cell totipotency by organizing mRNA regulatory machinery, including small RNA-based gene regulatory pathways. The C. elegans germ granule is compartmentalized into multiple subcompartments whose biological functions are largely unknown. Here, we identify an uncharted subcompartment of the C. elegans germ granule, which we term the E granule. The E granule is nonrandomly positioned within the germ granule. We identify five proteins that localize to the E granule, including the RNA-dependent RNA polymerase (RdRP) EGO-1, the Dicer-related helicase DRH-3, the Tudor domain-containing protein EKL-1, and two intrinsically disordered proteins, EGC-1 and ELLI-1. Localization of EGO-1 to the E granule enables synthesis of a specialized class of 22G RNAs, which derive exclusively from 5' regions of a subset of germline-expressed mRNAs. Defects in E granule assembly elicit disordered production of endogenous siRNAs, which disturbs fertility and the RNAi response. Our results define a distinct subcompartment of the C. elegans germ granule and suggest that one function of germ granule compartmentalization is to facilitate the localized production of specialized classes of small regulatory RNAs.
| S-EPMC11236994 | biostudies-literature
Project description:Multiple conserved structural cis-acting regulatory elements have been recognized both in the coding and untranslated regions (UTRs) of the hepatitis C virus (HCV) genome. For example, the cis-element 5BSL3.2 in the HCV-coding region has been predicted to use both its apical and internal loops to interact with the X RNA in the 3'-UTR, with the IIId domain in the 5'-UTR and with the Alt sequence in the coding region. Additionally, the X RNA region uses a palindromic sequence that overlaps the sequence required for the interaction with 5BSL3.2, to dimerize with another HCV genome. The ability of the 5BSL3.2 and X RNA regions to engage in multi-interactions suggests the existence of one or more molecular RNA switches which may regulate different steps of the HCV life cycle. In this study, we used biophysical methods to characterize the essential interactions of these HCV cis-elements at the molecular level. Our results indicate that X RNA interacts with 5BSL3.2 and another X RNA molecule by adopting two different conformations and that 5BSL3.2 engages simultaneously in kissing interactions using its apical and internal loops. Based on these results, we propose a mode of action for possible molecular switches involving the HCV RNA.
| S-EPMC3575821 | biostudies-literature
Project description:Engineered small molecule triggers are important tools for the control and investigation of biological processes, in particular protein function. Staudinger reductions of aryl azides to amines through the use of phosphines can trigger an elimination reaction, and thereby activation of a functional molecule, if an appropriately positioned leaving group is present. We conducted detailed investigations of the effect of aryl azide and phosphine structure on both the mechanism and kinetics of these reaction-induced eliminations and identified phosphine/azide pairs that enable complete activation within minutes under physiologically relevant conditions.
| S-EPMC6365568 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-05-01 | GSE112775 | GEO
Project description:An important requirement for achieving many goals of synthetic biology is the availability of a large repertoire of reprogrammable genetic switches and appropriate transmitter molecules. In addition to engineering genetic switches, the interconnection of individual switches becomes increasingly important for the construction of more complex genetic networks. In particular, RNA-based switches of gene expression have become a powerful tool to post-transcriptionally program genetic circuits. RNAs used for regulatory purposes have the advantage to transmit, sense, process and execute information. We have recently used the hammerhead ribozyme to control translation initiation in a small molecule-dependent fashion. In addition, riboregulators have been constructed in which a small RNA acts as transmitter molecule to control translation of a target mRNA. In this study, we combine both concepts and redesign the hammerhead ribozyme to sense small trans-acting RNAs (taRNAs) as input molecules resulting in repression of translation initiation in Escherichia coli. Importantly, our ribozyme-based expression platform is compatible with previously reported artificial taRNAs, which were reported to act as inducers of gene expression. In addition, we provide several insights into key requirements of riboregulatory systems, including the influences of varying transcriptional induction of the taRNA and mRNA transcripts, 5'-processing of taRNAs, as well as altering the secondary structure of the taRNA. In conclusion, we introduce an RNA-responsive ribozyme-based expression system to the field of artificial riboregulators that can serve as reprogrammable platform for engineering higher-order genetic circuits.
| S-EPMC3664830 | biostudies-literature