title: Base pairing interaction between 5'- and 3'-UTRs controls icaR mRNA translation in Staphylococcus aureus.
abstract: The presence of regulatory sequences in the 3' untranslated region (3'-UTR) of eukaryotic mRNAs controlling RNA stability and translation efficiency is widely recognized. In contrast, the relevance of 3'-UTRs in bacterial mRNA functionality has been disregarded. Here, we report evidences showing that around one-third of the mapped mRNAs of the major human pathogen Staphylococcus aureus carry 3'-UTRs longer than 100-nt and thus, potential regulatory functions. We selected the long 3'-UTR of icaR, which codes for the repressor of the main exopolysaccharidic compound of the S. aureus biofilm matrix, to evaluate the role that 3'-UTRs may play in controlling mRNA expression. We showed that base pairing between the 3'-UTR and the Shine-Dalgarno (SD) region of icaR mRNA interferes with the translation initiation complex and generates a double-stranded substrate for RNase III. Deletion or substitution of the motif (UCCCCUG) within icaR 3'-UTR was sufficient to abolish this interaction and resulted in the accumulation of IcaR repressor and inhibition of biofilm development. Our findings provide a singular example of a new potential post-transcriptional regulatory mechanism to modulate bacterial gene expression through the interaction of a 3'-UTR with the 5'-UTR of the same mRNA.
authors.affiliation: Laboratory of Microbial Biofilms. Instituto de Agrobiotecnología (IDAB). Universidad Pública de Navarra-CSIC-Gobierno de Navarra. Campus de Arrosadía. Pamplona, Spain.
authors.forename: Igor
authors.initials: I
authors.lastname: Ruiz de los Mozos
authors.affiliation: Laboratory of Microbial Biofilms. Instituto de Agrobiotecnología (IDAB). Universidad Pública de Navarra-CSIC-Gobierno de Navarra. Campus de Arrosadía. Pamplona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Vergara-Irigaray
authors.affiliation: Genomics, Proteomics and Bioinformatics Unit. Center for Applied Medical Research. University of Navarra. Pamplona, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Segura
authors.affiliation: Laboratory of Microbial Biofilms. Instituto de Agrobiotecnología (IDAB). Universidad Pública de Navarra-CSIC-Gobierno de Navarra. Campus de Arrosadía. Pamplona, Spain.
authors.forename: Maite
authors.initials: M
authors.lastname: Villanueva
authors.affiliation: Laboratory of Microbial Biofilms. Instituto de Agrobiotecnología (IDAB). Universidad Pública de Navarra-CSIC-Gobierno de Navarra. Campus de Arrosadía. Pamplona, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Bitarte
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa. Oeiras, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Saramago
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa. Oeiras, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Domingues
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa. Oeiras, Portugal.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Arraiano
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC. Strasbourg, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fechter
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC. Strasbourg, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Romby
authors.affiliation: Laboratory of Microbial Biofilms. Instituto de Agrobiotecnología (IDAB). Universidad Pública de Navarra-CSIC-Gobierno de Navarra. Campus de Arrosadía. Pamplona, Spain.
authors.forename: Jaione
authors.initials: J
authors.lastname: Valle
authors.affiliation: Laboratory of Microbial Biofilms. Instituto de Agrobiotecnología (IDAB). Universidad Pública de Navarra-CSIC-Gobierno de Navarra. Campus de Arrosadía. Pamplona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Solano
authors.affiliation: Laboratory of Microbial Biofilms. Instituto de Agrobiotecnología (IDAB). Universidad Pública de Navarra-CSIC-Gobierno de Navarra. Campus de Arrosadía. Pamplona, Spain.
authors.forename: Iñigo
authors.initials: I
authors.lastname: Lasa
authors.affiliation: Laboratory of Microbial Biofilms. Instituto de Agrobiotecnología (IDAB). Universidad Pública de Navarra-CSIC-Gobierno de Navarra. Campus de Arrosadía. Pamplona, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Toledo-Arana
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D020029:Base Pairing; D018441:Biofilms; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics*; D013203:Staphylococcal Infections / Q000235:genetics / Q000473:pathology; D013211:Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D012333:RNA, Messenger; D038621:Regulatory Sequences, Ribonucleic Acid