11 March 2026
Human Technopole has been awarded a €1.35 million Consolidator Grant from the Fondo Italiano per la Scienza (FIS3) to investigate how cells control the stability of messenger RNAs. The funding will support the POLARIS project, led by the Legnini Group, which aims to uncover the molecular principles governing the synthesis and regulation of poly(A) tails, a key feature that determines how long mRNA molecules survive and function inside cells.
Almost all eukaryotic messenger RNAs carry a stretch of repeated adenosine nucleotides at their end, known as the poly(A) tail. This structure plays a central role in gene expression: it helps mRNA molecules produce proteins and protects them from degradation. Yet its length varies widely and acts as a molecular timer that determines how long an mRNA remains active. Despite its importance, the mechanisms that establish and regulate poly(A) tail length remain poorly understood.
The POLARIS – Mechanisms and Regulatory Principles of Poly(A) Tails in the Control of mRNA Metabolism project will address this gap by investigating how poly(A) tails are synthesised, how their length is controlled, and how this process influences mRNA stability and thereby impact on higher cellular functions such as proliferation and differentiation. By linking biochemical mechanisms to cell function, the project aims to build a systematic understanding of how gene expression is regulated at the RNA level.
“Tail length control is central to gene expression and RNA metabolism, yet we still lack a clear understanding of how it is controlled,” says Ivano Legnini, Group Leader in the Genomics Research Centre at Human Technopole. “By combining innovative sequencing technologies with computational modelling, we aim to uncover the molecular logic governing poly(A) tails and how this control shapes cellular functions.”
To tackle these questions, the research will integrate biochemical and genetic approaches with advanced sequencing technologies capable of measuring poly(A) tails at high resolution. These experimental methods will be combined with computational modelling and artificial intelligence tools designed to identify the sequence features that influence mRNA stability. Together, these approaches will help decipher the regulatory code that determines how poly(A) tails are synthesised, shortened or extended over time.
The project will benefit from Human Technopole’s interdisciplinary environment and shared research infrastructure, including fundamental contributions from the National Facilities for Structural Biology, Genomics, Genome Engineering and Disease Modelling, and Light Imaging. A key collaboration with Florian Jug’s Group within the Scientific AI Flagship research programme will support the development of deep-learning approaches to interpret the regulatory code behind tail length control and RNA stability.
By uncovering how poly(A) tails regulate the stability of mRNA molecules, POLARIS aims to establish a new framework for understanding RNA metabolism. These insights could ultimately inform the design of future RNA-based technologies, including mRNA vaccines and RNA therapeutics. As part of Human Technopole’s broader mission to investigate biological systems across scales and translate fundamental discoveries into advances for medicine, the project illustrates how basic research can open new paths towards improving human health.
The POLARIS project is funded by the Italian Ministry of University and Research (MUR) under the FIS3 Fondo Italiano della Scienza programme (FIS-2024-04993, CUP B53C25003890001).
Discover here the open job positions related to this project.
