Société Française de Biochimie et Biologie Moléculaire

Silvia Bottini-October 2018

INSERM U1065 C3M, Team control of gene expression Nice, FrancePost-transcriptional gene silencing mediated by microRNAs is controlled by nucleoplasmic Sfpq Nat Commun. 2017 Oct 30;8(1):1189. doi: 10.1038/s41467-017-01126-x Bottini S, Hamouda-Tekaya N, Mategot R, Zaragosi LE, Audebert S, Pisano S, Grandjean V, Mauduit C, Benahmed M, Barbry P, Repetto E, Trabucchi M.


"Silvia Bottini, 33 years old, is a post-doctoral research associate at the Inserm U1065 since four years. Her research interests are focused on the characterization and the development of novel bioinformatics approaches to identify and uncover the features governing the RNA-protein interaction network both in vitro and in vivo systems. She did her PhD in Bioinformatics at the University of Siena (Italy) in the laboratory of Genomics of Novartis Vaccines Company headed by Dr. Claudio Donati, under the supervision of Dr. Alessandro Muzzi. She developed a computational pipeline, called “PIPE-chipSAD”, for bacterial transcriptome studies based on high-density microarray experiments that integrates the analysis of the hybridization signal with the genomic position of probes and identifies transcript boundaries. In October 2014, she joined Dr. Michele Trabucchi’s team at the “Centre Méditerranéen de Médecine Moléculaire” (Inserm U1065) in Nice to investigate the molecular mechanisms of regulated gene expression by miRNAs. Specifically, her works in Trabucchi’s team allowed to extend the miRNA-mediated post-transcriptional gene silencing into the nucleoplasm by demonstrating that the nucleoplasmic RNA-binding protein Sfpq controls miRNA activity in RNA-dependent fashion."


Silvia Bottini, PhD
Control of Gene Expression INSERM U1065, C3M
University of Nice Sophia-Antipolis
151, route de St-Antoine-de-Ginestière
B.P. 2 3194
06204 - NICE CEDEX 3
Phone +33-489-0642-56


There is a growing body of evidence about the presence and the activity of the miRISC in the nucleus of mammalian cells. Here, we show by quantitative proteomic analysis that Ago2 interacts with the nucleoplasmic protein Sfpq in an RNA-dependent fashion. By a combination of HITS-CLIP and transcriptomic analyses, we demonstrate that Sfpq directly controls the miRNA targeting of a subset of binding sites by local binding. Sfpq modulates miRNA targeting in both nucleoplasm and cytoplasm, indicating a nucleoplasmic commitment of Sfpq-target mRNAs that globally influences miRNA modes of action. Mechanistically, Sfpq binds to a sizeable set of long 3'UTRs forming aggregates to optimize miRNA positioning/recruitment at selected binding sites, including let-7a binding to Lin28A 3'UTR. Our results extend the miRNA-mediated post-transcriptional gene silencing into the nucleoplasm and indicate that an Sfpq-dependent strategy for controlling miRNA activity takes place in cells, contributing to the complexity of miRNA-dependent gene expression control.