Mechanisms Used for Genomic Proliferation by Thermophilic Group II Introns

Studies of mobile group II introns from a thermophilic cyanobacterium reveal how these introns proliferate within genomes and might explain the origin of introns and retroelements in higher organisms

The Retrohoming of Linear Group II Intron RNAs in Drosophila melanogaster Occurs by Both DNA Ligase 4–Dependent and –Independent Mechanisms

Mobile group II introns are bacterial retrotransposons that are thought to have invaded early eukaryotes and evolved into introns and retroelements in higher organisms. In bacteria, group II introns typically retrohome via full reverse splicing of an excised intron lariat RNA into a DNA site, where it is reverse transcribed by the intron-encoded protein. Recently, we showed that linear group II intron RNAs, which can result from hydrolytic splicing or debranching of lariat RNAs, can retrohome in eukaryotes by performing only the first step of reverse splicing, ligating their 3′ end to the downstream DNA exon. Reverse transcription then yields an intron cDNA, whose free end is linked to the upstream DNA exon by an error-prone process that yields junctions similar to those formed by non-homologous end joining (NHEJ). Here, by using Drosophila melanogaster NHEJ mutants, we show that linear intron RNA retrohoming occurs by major Lig4-dependent and minor Lig4-independent mechanisms, which appear to be related to classical and alternate NHEJ, respectively. The DNA repair polymerase θ plays a crucial role in both pathways. Surprisingly, however, mutations in Ku70, which functions in capping chromosome ends during NHEJ, have only moderate, possibly indirect effects, suggesting that both Lig4 and the alternate end-joining ligase act in some retrohoming events independently of Ku. Another potential Lig4-independent mechanism, reverse transcriptase template switching from the intron RNA to the upstream exon DNA, occurs in vitro, but gives junctions differing from the majority in vivo. Our results show that group II introns can utilize cellular NHEJ enzymes for retromobility in higher organisms, possibly exploiting mechanisms that contribute to retrotransposition and mitigate DNA damage by resident retrotransposons. Additionally, our results reveal novel activities of group II intron reverse transcriptases, with implications for retrohoming mechanisms and potential biotechnological applications

Learning to live together: mutualism between self-splicing introns and their hosts

Group I and II introns can be considered as molecular parasites that interrupt protein-coding and structural RNA genes in all domains of life. They function as self-splicing ribozymes and thereby limit the phenotypic costs associated with disruption of a host gene while they act as mobile DNA elements to promote their spread within and between genomes. Once considered purely selfish DNA elements, they now seem, in the light of recent work on the molecular mechanisms regulating bacterial and phage group I and II intron dynamics, to show evidence of co-evolution with their hosts. These previously underappreciated relationships serve the co-evolving entities particularly well in times of environmental stress

Central administration of cholecystokinin stimulates gastric pepsinogen secretion from anaesthetized rats.

Intracerebroventricular administration of CCK-8S was associated with a stimulation of gastric pepsinogen secretion from anaesthetized rats; similar effects were induced by CCK-8S given intravenously. The excitatory effect of intracerebroventricular CCK-8S was not modified by central injection of L-364,718 or L-365,260, whereas both these antagonists, given by intravenous route, prevented the pepsigogue action of parenteral CCK-8S. Intracerebroventricular or intravenous CCK-8S also increased basal acid secretion, this latter effect being prevented by parenteral L-365,260 but not L-364,718. It is suggested that centrally applied CCK-8S evokes pepsinogen secretion through the activation of peripheral CCK-A and CCK-B receptors

Suramin enhances ethanol-induced injury to gastric mucosa in rats.

Suramin is currently used in clinical practice as antineoplastic agent because of its complex interaction with the biological activity of various growth factors involved in tumor progression. The influence exerted by suramin on gastric injury induced in rats by intraluminal injection of absolute ethanol was investigated in the present study. The morphometric analysis of gastric histological sections revealed that suramin, 18 mg/kg, administered intraperitoneally for 14 days every other day, caused a marked enhancement of ethanol-induced mucosal damage. This effect was more pronounced 1-8 hr following ethanol administration, and it was still significant after 48 hr. In suramin-treated animals the evaluation of Alcian blue recovery from gastric-bound mucus showed that the levels of adherent mucus were significantly lower than those detected in untreated rats. In addition, pretreatment with suramin did not modify basal acid secretion, but caused potentiation of acid output stimulated by pylorus ligation or electrical vagal stimulation. Overall, the present results indicate that suramin exerts a negative influence on both gastric protective and repairing mechanisms. Due to the peculiar pharmacodynamic profile of suramin, it is suggested that interference with endogenous growth factors, endowed with physiological protective activity on gastric mucosa, might account for the damage-enhancing action of this drug