Biology subjects

Cicconetti, C.

Publications and source records attributed to Cicconetti, C..

2 recordsLinked to original sources

bioRxiv2023

ZZZ3 protects human embryonic stem cells from nucleolar stress by boosting mTOR/ribosome pathway.

Embryonic stem cells (ESCs) are defined as stem cells with self-renewing and differentiation capabilities. These unique properties are tightly regulated and controlled by complex genetic and molecular mechanisms whose understanding is essential for both basic and translational research. A large number of studies have mostly focused on understanding the molecular mechanisms governing pluripotency and differentiation of ESCs, while the regulation of proliferation has received comparably less attention. In mouse ESCs, pluripotency and proliferation can be independent processes meaning that it is possible for mouse ESCs to maintain their pluripotent state without actively proliferating. Here, we investigate the role of ZZZ3 (Zinc Finger ZZ-Type Containing 3) function in human ESCs homeostasis. We found that knockdown of ZZZ3 strongly decreases ribosome biogenesis, translation, and mTOR signaling leading to nucleolar stress and significant reduction of cell proliferation. This process occurs without affecting pluripotency, suggesting that ZZZ3-depleted ESCs enter a dormant-like state and that proliferation and pluripotency can be uncoupled also in human ESCs.

molecular biology↗

bioRxiv2022

RNABSdb and 3plex enable deep computational investigation of triplex forming lncRNAs

1.Long non-coding RNAs (lncRNAs) regulate gene expression through different molecular mechanisms, including DNA binding. We curated the first database of RNA Binding Sites (RNABSdb) by harmonising publicly available raw-data of RNA-DNA binding experiments. This resource is crucial to enable systematic studies on transcriptional regulation driven by lncRNAs. Focusing on high quality experiments, we find that the number of binding sites for each lncRNAs varies from hundreds to tens of thousands. Despite being poorly characterised, the formation of RNA:DNA:DNA triple helices (TPXs) is one of the molecular mechanisms that allows lncRNAs to bind the genome and regulate gene expression. We developed 3plex, a software able to predict TPXs in silico. We show that 3plex outperforms previous existing approaches leveraging the data collected in RNABSdb for lncRNAs known to form functional TPXs. Moreover this analysis shows that TPXs tend to be shorter and more degenerated than previously expected. Finally, we applied 3plex to all the lncRNAs collected in RNABSdb and we show that the majority of them could directly bind the genome by TPXs formation. Data and software are available at https://molinerislab.github.io/RNABSdb/ and https://github.com/molinerisLab/3plex.

bioinformatics↗