Human serine hydroxymethyltransferase (SHMT) regulates the serine-glycine one carbon metabolism and plays a role in cancer metabolic reprogramming. Two SHMT isozymes are acting in the cell: SHMT1 encoding the cytoplasmic isozyme, and SHMT2 encoding the mitochondrial one. Here we present a molecular model built on experimental data reporting the interaction between SHMT1 protein and SHMT2 mRNA, recently discovered in lung cancer cells. Using a stochastic dynamic model, we show that RNA moieties dynamically regulate serine and glycine concentration, shaping the system behaviour. For the first time we observe an active functional role of the RNA in the regulation of the serine-glycine metabolism and availability, which unravels a complex layer of regulation that cancer cells exploit to fine tune amino acids availability according to their metabolic needs. The quantitative model, complemented by an experimental validation in the lung adenocarcinoma cell line H1299, exploits RNA molecules as metabolic switches of the SHMT1 activity. Our results pave the way for the development of RNA-based molecules able to unbalance serine metabolism in cancer cells.

Modelling of SHMT1 riboregulation predicts dynamic changes of serine and glycine levels across cellular compartments / Monti, Michele; Guiducci, Giulia; Paone, Alessio; Rinaldo, Serena; Giardina, Giorgio; Liberati, Francesca Romana; Cutruzzolá, Francesca; Tartaglia, Gian Gaetano. - In: COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL. - ISSN 2001-0370. - 19:(2021), pp. 3034-3041. [10.1016/j.csbj.2021.05.019]

Modelling of SHMT1 riboregulation predicts dynamic changes of serine and glycine levels across cellular compartments

Paone, Alessio;Rinaldo, Serena;Giardina, Giorgio;Liberati, Francesca Romana;Cutruzzolá, Francesca
;
Tartaglia, Gian Gaetano
2021

Abstract

Human serine hydroxymethyltransferase (SHMT) regulates the serine-glycine one carbon metabolism and plays a role in cancer metabolic reprogramming. Two SHMT isozymes are acting in the cell: SHMT1 encoding the cytoplasmic isozyme, and SHMT2 encoding the mitochondrial one. Here we present a molecular model built on experimental data reporting the interaction between SHMT1 protein and SHMT2 mRNA, recently discovered in lung cancer cells. Using a stochastic dynamic model, we show that RNA moieties dynamically regulate serine and glycine concentration, shaping the system behaviour. For the first time we observe an active functional role of the RNA in the regulation of the serine-glycine metabolism and availability, which unravels a complex layer of regulation that cancer cells exploit to fine tune amino acids availability according to their metabolic needs. The quantitative model, complemented by an experimental validation in the lung adenocarcinoma cell line H1299, exploits RNA molecules as metabolic switches of the SHMT1 activity. Our results pave the way for the development of RNA-based molecules able to unbalance serine metabolism in cancer cells.
2021
Serine/Glycine metabolism; RNA-binding protein; RNA-protein interactions; Metabolic networks
01 Pubblicazione su rivista::01a Articolo in rivista
Modelling of SHMT1 riboregulation predicts dynamic changes of serine and glycine levels across cellular compartments / Monti, Michele; Guiducci, Giulia; Paone, Alessio; Rinaldo, Serena; Giardina, Giorgio; Liberati, Francesca Romana; Cutruzzolá, Francesca; Tartaglia, Gian Gaetano. - In: COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL. - ISSN 2001-0370. - 19:(2021), pp. 3034-3041. [10.1016/j.csbj.2021.05.019]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1551300
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