The moonlighting RNA-binding activity of cytosolic serine hydroxymethyltransferase contributes to control compartmentalization of serine metabolism

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Guiducci, Giulia
  • dc.contributor.author Paone, Alessio
  • dc.contributor.author Tramonti, Angela
  • dc.contributor.author Giardina, Giorgio
  • dc.contributor.author Rinaldo, Serena
  • dc.contributor.author Bouzidi, Amani
  • dc.contributor.author Magnifico, Maria C.
  • dc.contributor.author Marani, Marina
  • dc.contributor.author Menendez, Javier A.
  • dc.contributor.author Fatica, Alessandro
  • dc.contributor.author Macone, Alberto
  • dc.contributor.author Armaos, Alexandros, 1989-
  • dc.contributor.author Tartaglia, Gian Gaetano
  • dc.contributor.author Contestabile, Roberto
  • dc.contributor.author Paiardini, Alessandro
  • dc.contributor.author Cutruzzolà, Francesca
  • dc.date.accessioned 2019-07-30T07:42:36Z
  • dc.date.available 2019-07-30T07:42:36Z
  • dc.date.issued 2019
  • dc.description.abstract Enzymes of intermediary metabolism are often reported to have moonlighting functions as RNA-binding proteins and have regulatory roles beyond their primary activities. Human serine hydroxymethyltransferase (SHMT) is essential for the one-carbon metabolism, which sustains growth and proliferation in normal and tumour cells. Here, we characterize the RNA-binding function of cytosolic SHMT (SHMT1) in vitro and using cancer cell models. We show that SHMT1 controls the expression of its mitochondrial counterpart (SHMT2) by binding to the 5'untranslated region of the SHMT2 transcript (UTR2). Importantly, binding to RNA is modulated by metabolites in vitro and the formation of the SHMT1-UTR2 complex inhibits the serine cleavage activity of the SHMT1, without affecting the reverse reaction. Transfection of UTR2 in cancer cells controls SHMT1 activity and reduces cell viability. We propose a novel mechanism of SHMT regulation, which interconnects RNA and metabolites levels to control the cross-talk between cytosolic and mitochondrial compartments of serine metabolism.
  • dc.description.sponsorship Associazione Italiana per la Ricerca sul Cancro [AIRC-IG2015 n. 16720 to F.C., AIRC-MFAG2017 n. 20447 to A.P.); Sapienza University of Rome [RM11715C646D693E to S.R.; RP11715C644A5CCE, GA116154C8A94E3D to F.C.]; Istituto-Pasteur Italia-Fondazione Cenci Bolognetti [Grant 2015 to F.C.]; European Research Council [RIBOMYLOME_309545 to G.G.T.]; Spanish Ministry of Economy and Competitiveness [BFU2014-55054-P, BFU2017-86970-P]; ‘Fundació La Marató de TV3’ [PI043296]; Ministerio de Ciencia e Innovación (Plan Nacional de I+D+I, Spain) [SAF2016-80639-P to J.A.M.]. Funding for open access charge: Associazione Italiana per la Ricerca sul Cancro [AIRC-IG2015 n. 16720]
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Guiducci G, Paone A, Tramonti A, Giardina G, Rinaldo S, Bouzidi A et al. The moonlighting RNA-binding activity of cytosolic serine hydroxymethyltransferase contributes to control compartmentalization of serine metabolism. Nucleic Acids Res. 2019 May 7;47(8):4240-54. DOI: 10.1093/nar/gkz129
  • dc.identifier.doi http://dx.doi.org/10.1093/nar/gkz129
  • dc.identifier.issn 0305-1048
  • dc.identifier.uri http://hdl.handle.net/10230/42201
  • dc.language.iso eng
  • dc.publisher Oxford University Press
  • dc.relation.ispartof Nucleic Acids Research. 2019 May 7;47(8):4240-54
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/309545
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-55054-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-86970-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-80639-P
  • dc.rights © 2019. Giulia Guiducci et al. Published by Oxford University Press. This is an Open Access article distributed under the terms of a Creative Commons Attribution License
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Proteïnes
  • dc.subject.other RNA
  • dc.subject.other Genètica
  • dc.subject.other Cèl·lules canceroses
  • dc.title The moonlighting RNA-binding activity of cytosolic serine hydroxymethyltransferase contributes to control compartmentalization of serine metabolism
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Center for Genomic Regulation (CRG))
Articles (Departament de Medicina i Ciències de la Vida)