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Piccinno, R.

Publications and source records attributed to Piccinno, R..

3 recordsLinked to original sources

Spiroplasma impairs testes gene expression in Glossina fuscipes fuscipes

Glossina fuscipes fuscipes is a riverine tsetse fly species, the primary vector of human and animal trypanosomiasis in Sub-Saharan Africa. Controlling tsetse fly populations is crucial for mitigating the socio-economic impact of this disease, as effective treatments remain challenging. Indeed, the development of control strategies is hindered by the species unique reproductive biology: adenotrophic viviparity, in which the female retains and nourishes the developing larva in her uterus throughout the pregnancy. The discovery of Spiroplasma in some G. f. fuscipes populations has drawn attention as a potential tool to enhance tsetse fly control strategies. Although Spiroplasma does not exhibit in G. f. fuscipes the male-killing phenotype observed in Drosophila melanogaster, evidence suggests that it may confer refractoriness to Trypanosoma infection. This has led to further investigations into its broader effects on G. f. fuscipes biology, particularly its potential impact on Glossina reproductive fitness. In this study, we considered Spiroplasma effect on the male reproduction. For this, we performed a differential gene expression analysis on testes and male accessory glands (MAGs) between Spiroplasma-infected and uninfected males. A significant downregulation of genes was observed in testes while a minor effect has been detected on MAGs. Downregulation of testes genes associated with functions related to sperm motility, energy metabolism, and mitochondrial function has been observed. Additionally, differentially expressed genes involved in antimicrobial activity and circadian rhythm regulation were observed. These findings provide valuable insights into the potential fitness costs of Spiroplasma infection for the fly and its implications for the bacterium use as biological control strategies targeting G. f. fuscipes.

genomics↗

The INO80 remodeler couples premature termination of mRNA synthesis with transcription elongation

Co-transcriptional RNA quality control is essential for gene expression. However, its regulation remains poorly understood. Here, we report that the evolutionarily conserved ATP-dependent chromatin remodelling INO80 complex promotes transcription termination by the non-coding RNA quality control pathway in S. cerevisiae. Loss of INO80 leads to accumulation of stalled RNA Polymerase II preferentially at promoter-proximal pausing sites, compromising Pol II processivity and hindering transcription elongation. We reveal that binding of RNA surveillance and non-coding transcription termination factors to promoter-proximal mRNA regions is associated with increased promoter-proximal pausing. INO80 counteracts promoter-proximal stalling of genes attenuated by the Nrd1-Nab3-Sen1 (NNS) non-coding transcription termination complex, promoting their expression. We show that INO80 interacts with Nrd1 and the Nab2 RNA surveillance factor in vivo. Absence of INO80 leads to defective transcription termination by the Nrd1-Nab3-Sen1 (NNS) complex. We demonstrate that INO80 facilitates the recruitment of Nab2 at non-coding transcription termination sites and its association with promoter-proximally terminated mRNA transcripts. Finally, we provide evidence that INO80 promotes the release of stalled RNA Polymerase II from a non-coding transcription termination site. Collectively, our work suggests that the INO80 complex regulates transcription by removal of stalled Polymerase, implicating a chromatin-based mechanism for non-coding and premature transcription termination in gene expression.

molecular biology↗

Spatial chromosome folding and active transcription drive DNA fragility and formation of oncogenic MLL translocations

How spatial chromosome organization influences genome integrity is still poorly understood. Here we show that DNA double-strand breaks (DSBs) mediated by topoisomerase 2 (TOP2) activities, are enriched at chromatin loop anchors with high transcriptional activity. Recurrent DSBs occur at CTCF/cohesin bound sites at the bases of chromatin loops and their frequency positively correlates with transcriptional output and directionality. The physiological relevance of this preferential positioning is indicated by the finding that genes recurrently translocating to drive leukemias, are highly transcribed and are enriched at loop anchors. These genes accumulate DSBs at recurrent hot spots that give rise to chromosomal fusions relying on the activity of both TOP2 isoforms and on transcriptional elongation. We propose that transcription and 3D chromosome folding jointly pose a threat to genomic stability, and are key contributors to the occurrence of genome rearrangements that drive cancer.

cell biology↗