1,721,352 research outputs found
Guest editor special issue Novel Molecular Mechanisms Underlying Tumorigenesis and Innovative Therapeutic Approaches for Cancer-Fighting
No full textAS-NMD in ribosomal protein gene regulation: involvment of hnRNP H1. KHSRP and Nucleophosmin/NMP
No full textNonsense-mediated mRNA Decay (NMD) is an mRNA quality-control mechanism that selectively recognizes and degrades aberrant transcripts harboring a premature termination codon (PTC), which could result from DNA mutation or from errors occurred during RNA metabolism. NMD could prevent the production of deleterious C-terminal truncated proteins (Chang et al., 2007). The highly conservation of NMD pathway through evolution suggests that it could play a more relevant biological role in the post-transcriptional regulation of gene expression rather than just degradation of PTC-harboring mRNAs. Indeed, many eukaryotic genes are regulated by the association between alternative splicing and NMD (AS-NMD): the alternative splicing would produce an unproductive mRNA isoform that harbors a PTC; NMD, which degrades the aberrant transcript, may modulate the RNA levels and, thus, the corresponding protein amount in the cell. Ribosomal protein genes represent a good model to study post-transcriptional regulation by AS-NMD. Ribosomal protein L3 (rpL3) pre-mRNA can undergo a canonical splicing, which produces an isoform properly translated into protein, or an alternative event, that produces a PTC-harboring isoform eliminated by NMD. It was demonstrated that free rpL3 protein (i.e. the ribosomal protein not involved in ribosome formation) regulates the rpL3 pre-mRNA splicing. In physiological condition, canonical splicing prevails over the alternative event. When there is an excess of rpL3 protein in the cell, the alternative splicing event is favoured, thus leading to a decrease of protein amount (Cuccurese et al., 2005). The aim of this project is to clarify the molecular mechanism of the post-transcriptional regulation of rpL3 gene through the splice site selection that leads to canonical or alternative isoform production. Since it was demonstrated that rpL3 is not able to interact directly with its pre-mRNA, rpL3 protein and pre-mRNA interactors in vitro were identified. Among these, I have investigated the role of two splicing factors, heterogeneous nuclear RiboNucleoProtein H1 (hnRNP H1) and K-homology splicing regulator protein (KHSRP), and of the nucleolar phosphoprotein Nucleophosmin/NPM on the rpL3 pre-mRNA splicing. These three proteins are involved in several phases of mRNA processing
Post-transcriptional regulatory strategies and extraribosomal functions of human rpL3
No full textrpL3 gene produces in addition to canonical mRNA isoform normally translated in protein, an alternative isoform, containing a PTC (premature termination codon) degraded by NMD (Nonsense mediated mRNA decay).
Moreover, overexpression of rpL3 causes an increase of alternative isoform level, unproductive, which results in rpL3 decrease. This negative feedback loop triggered by the accumulation of ribosomal protein, is a strategy that finely regulates the amount of ribosomal protein to an appropriate level, especially relevant to any extra-ribosomal functions of rpL3.
hnRNP H1, NPM and KHSRP are involved with different roles in the post-transcriptional regulation of rpL3 gene and we hypothesize a model of regulation that provides a sequence of interactions between these proteins and rpL3 transcript.
This post-transcriptional regulation, that provides the association of alternative splicing and NMD, can be very important to finely modulate the rpL3 amount available to extra-ribosomal functions
La scuola sulla pelle. I gessi dell’Accademia Carrara e alcune riflessioni sulla loro conservazione, tra estetica e storia
No full textThe paper opens with an examination of the collection of plaster casts held at the Accademia Carrara, originating from the art school that once formed an integral part of the institution, now functioning as a museum. Within the framework of the research project dedicated to the reassessment and conservation of this segment of the collection, a series of questions emerges concerning the most appropriate restoration methodologies. These revolve around the attempt to negotiate a balance between preserving the material traces resulting from the casts’ historical use as pedagogical tools and fulfilling the demands associated with their contemporary museological display
Meccanismi di splicing alternativo e nonsense mediated mRNA decay (NMD) nella regolazione dell'espressione di geni per proteine ribosomali umane
No full text
Regolazione post-trascrizionale della espressione genica mediante localizzazione di mRNA
No full textRibosomal Proteins Control or Bypass p53 during Nucleolar Stress
No full textThe nucleolus is the site of ribosome biogenesis, a complex process that requires the coordinate activity of all three RNA polymerases and hundreds of non-ribosomal factors that participate in the maturation of ribosomal RNA (rRNA) and assembly of small and large subunits. Nevertheless, emerging studies have highlighted the fundamental role of the nucleolus in sensing a variety of cellular stress stimuli that target ribosome biogenesis. This condition is known as nucleolar stress and triggers several response pathways to maintain cell homeostasis, either p53-dependent or p53-independent. The mouse double minute (MDM2)-p53 stress signaling pathways are activated by multiple signals and are among the most important regulators of cellular homeostasis. In this review, we will focus on the role of ribosomal proteins in p53-dependent and p53-independent response to nucleolar stress considering novel identified regulators of these pathways. We describe, in particular, the role of ribosomal protein uL3 (rpL3) in p53-independent nucleolar stress signaling pathways
- …
