Intronic and intergenic inverted repeats form dsRNA that activate RNase L but escape detection from the IFN system
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE143638 | GEO | 2021/01/13
REPOSITORIES: GEO
Similar Datasets
Project description:Intronic and intergenic inverted repeats form dsRNA that activate RNase L but escape detection from the IFN system
| PRJNA601163 | ENA
Project description:Impediments to DNA replication are known to induce gross chromosomal rearrangements (GCRs) and copy-number variations (CNVs). GCRs and CNVs underlie human genomic disorders and are a feature of cancer. During cancer development, environmental factors and oncogene-driven proliferation promote replication stress. Resulting GCRs and CNVs are proposed to contribute to cancer development and therapy resistance. When stress arrests replication, the replisome remains associated with the fork DNA (stalled fork) and is protected by the inter-S-phase checkpoint. Stalled forks efficiently resume when the stress is relieved. However, if the polymerases dissociate from the fork (fork collapse) or the fork structure breaks (broken fork), replication restart can proceed either by homologous recombination or microhomology-primed re-initiation. Here we ascertain the consequences of replication with a fork restarted by homologous recombination in fission yeast. We identify a new mechanism of chromosomal rearrangement through the observation that recombination-restarted forks have a considerably high propensity to execute a U-turn at small inverted repeats (up to 1 in 40 replication events). We propose that the error-prone nature of restarted forks contributes to the generation of GCRs and gene amplification in cancer, and to non-recurrent CNVs in genomic disorders.
| S-EPMC3605775 | biostudies-literature
Project description:Double-stranded RNA (dsRNA) can induce post-transcriptional gene silencing in a wide variety of organisms. Commonly, inverted repeats are used to produce dsRNA to silence genes of interest. However, cloning inverted repeats still remains a rate-limiting step for widely applying this technique. Here we describe a pGEM-T-based vector, pGEM-WIZ, designed to produce inverted repeats for any Drosophila gene. pGEM-WIZ has a high efficiency in assembling inverted repeats and the repeats in this vector are stable in regular Escherichia coli strains. Furthermore, we have developed a method for rapid selection of clones with an inverted repeat based on size and relative copy number of the vector with or without an insert. This method further eases the cloning process. The inverted repeat cassette assembled in pGEM-WIZ can be easily transferred to commonly available expression vectors suitable for stably expressing inverted repeats in vitro and in vivo.
| S-EPMC1624905 | biostudies-literature
Project description:This work aims to describe the observed enrichment of inverted repeats in the human genome; and to identify and describe, with detailed length profiles, the regions with significant and relevant enriched occurrence of inverted repeats. The enrichment is assessed and tested with a recently proposed measure (z-scores based measure). We simulate a genome using an order 7 Markov model trained with the data from the real genome. The simulated genome is used to establish the critical values which are used as decision thresholds to identify the regions with significant enriched concentrations. Several human genome regions are highly enriched in the occurrence of inverted repeats. This is observed in all the human chromosomes. The distribution of inverted repeat lengths varies along the genome. The majority of the regions with severely exaggerated enrichment contain mainly short length inverted repeats. There are also regions with regular peaks along the inverted repeats lengths distribution (periodic regularities) and other regions with exaggerated enrichment for long lengths (less frequent). However, adjacent regions tend to have similar distributions.
| S-EPMC10561070 | biostudies-literature
Project description:Ribonucleases (RNases) play a critical role in RNA processing and degradation by hydrolyzing phosphodiester bonds (exo- or endonucleolytically). Many RNases that cut RNA internally exhibit substrate specificity, but their target sites are usually limited to one or a few specific nucleotides in single-stranded RNA and often in a context of a particular three-dimensional structure of the substrate. Thus far, no RNase counterparts of restriction enzymes have been identified which could cleave double-stranded RNA (dsRNA) in a sequence-specific manner. Here, we present evidence for a sequence-dependent cleavage of long dsRNA by RNase Mini-III from Bacillus subtilis (BsMiniIII). Analysis of the sites cleaved by this enzyme in limited digest of bacteriophage Φ6 dsRNA led to the identification of a consensus target sequence. We defined nucleotide residues within the preferred cleavage site that affected the efficiency of the cleavage and were essential for the discrimination of cleavable versus non-cleavable dsRNA sequences. We have also determined that the loop α5b-α6, a distinctive structural element in Mini-III RNases, is crucial for the specific cleavage, but not for dsRNA binding. Our results suggest that BsMiniIII may serve as a prototype of a sequence-specific dsRNase that could possibly be used for targeted cleavage of dsRNA.
| S-EPMC4357697 | biostudies-literature
Project description:IS5075 and IS4321 are closely related (93.1% identical) members of the IS1111 family that target a specific position in the 38-bp terminal inverted repeats of Tn21 family transposons and that are inserted in only one orientation. They are 1,327 bp long and have identical ends consisting of short inverted repeats of 12 bp with an additional 7 bp (TAATGAG) or 6 bp (AATGAG) to the left of the left inverted repeats and 3 bp (AGA) or 4 bp (AGAT) to the right of the right inverted repeat. Circular forms of IS5075 and IS4321 in which the inverted repeats are separated by abutting terminal sequences (AGATAATGAG) were detected. A similar circular product was found for the related ISPa11. Transposition of IS4321 into the 38-bp target site was detected, but a flanking duplication was not generated. The precisely reconstituted target site was also identified. Over 50 members of the IS1111 family were identified. They encode related transposases, have related inverted repeats, and include related bases that lie outside these inverted repeats. In some, the flanking bases number 5 or 6 on the left and 4 or 3 on the right. Specific target sites were found for several of these insertion sequence (IS) elements. IS1111 family members therefore differ from the majority of IS elements, which are characterized by terminal inverted repeats and a target site duplication, and from members of the related IS110 family, which do not have obvious inverted repeats near their termini.
| S-EPMC219399 | biostudies-literature
Project description:The mobile element IS30 has 26-bp imperfect terminal inverted repeats (IRs) that are indispensable for transposition. We have analyzed the effects of IR mutations on both major transposition steps, the circle formation and integration of the abutted ends, characteristic for IS30. Several mutants show strikingly different phenotypes if the mutations are present at one or both ends and differentially influence the transposition steps. The two IRs are equivalent in the recombination reactions and contain several functional regions. We have determined that positions 20 to 26 are responsible for binding of the N-terminal domain of the transposase and the formation of a correct 2-bp spacer between the abutted ends. However, integration is efficient without this region, suggesting that a second binding site for the transposase may exist, possibly within the region from 4 to 11 bp. Several mutations at this part of the IRs, which are highly conserved in the IS30 family, considerably affected both major transposition steps. In addition, positions 16 and 17 seem to be responsible for distinguishing the IRs of related insertion sequences by providing specificity for the transposase to recognize its cognate ends. Finally, we show both in vivo and in vitro that position 3 has a determining role in the donor function of the ends, especially in DNA cleavage adjacent to the IRs. Taken together, the present work provides evidence for a more complex organization of the IS30 IRs than was previously suggested.
| S-EPMC2897661 | biostudies-literature
Project description:Inverted repeats (IRs) serve as potential biomarkers for genomic instability, DNA replication and other genetic processes. However, little information can be found in databases to help researchers recognize potential IR nucleotides, explore junction sites and annotate related functional genes. Plant Chloroplast Inverted Repeats (PCIR) is an interactive, web-based platform containing various sequenced chloroplast genomes that enables detection, searching and visualization of large-scale detailed information on IRs. PCIR contains many datasets, including 21 433 IRs, 113 plants chloroplast genomes, 16 948 functional genes and 21 659 visual maps. This database offers an online prediction tool for detecting IRs based on DNA sequences. PCIR can also analyze phylogenetic relationships using IR information among different species and provide users with high-quality marker maps. This database will be a valuable resource for IR distribution patterns, related genes and architectural features.
| S-EPMC6835207 | biostudies-literature
Project description:Photosynthetic euglenids (Euglenophyta) are a monophyletic group of unicellular eukaryotes characterized by the presence of plastids, which arose as the result of the secondary endosymbiosis. Many Euglenophyta plastid (pt) genomes have been characterized recently, but they represented mainly one family - Euglenaceae. Here, we report a comparative analysis of plastid genomes from eight representatives of the family Phacaceae. Newly sequenced plastid genomes share a number of features including synteny and gene content, except for genes mat2 and mat5 encoding maturases. The observed diversity of intron number and presence/absence of maturases corroborated previously suggested correlation between the number of maturases in the pt genome and intron proliferation. Surprisingly, pt genomes of taxa belonging to Discoplastis and Lepocinclis encode two inverted repeat (IR) regions containing the rDNA operon, which are absent from the Euglenaceae. By mapping the presence/absence of IR region on the obtained phylogenomic tree, we reconstructed the most probable events in the evolution of IRs in the Euglenophyta. Our study highlights the dynamic nature of the Euglenophyta plastid genome, in particular with regards to the IR regions that underwent losses repeatedly.
| S-EPMC6207741 | biostudies-literature
Project description:Symporters are membrane proteins that couple energy stored in electrochemical potential gradients to drive the cotransport of molecules and ions into cells. Traditionally, proteins are classified into gene families based on sequence homology and functional properties, for example the sodium glucose (SLC5 or Sodium Solute Symporter Family, SSS or SSF) and GABA (SLC6 or Neurotransmitter Sodium Symporter Family, NSS or SNF) symporter families [1-4]. Recently, it has been established that four Na(+)-symporter proteins with unrelated sequences have a common structural core containing an inverted repeat of 5 transmembrane (TM) helices [5(**)-8(**)]. Analysis of these four structures reveals that they reside in different conformations along the transport cycle providing atomic insight into the mechanism of sodium solute cotransport.
| S-EPMC3496787 | biostudies-literature