Base Pairing Interaction between 5′- and 3′-UTRs Controls icaR mRNA Translation in Staphylococcus aureus

• Published in: PLoS genetics Vol. 9; no. 12; p. e1004001
• Main Authors: Ruiz de los Mozos, Igor, Vergara-Irigaray, Marta, Segura, Victor, Villanueva, Maite, Bitarte, Nerea, Saramago, Margarida, Domingues, Susana, Arraiano, Cecilia M., Fechter, Pierre, Romby, Pascale, Valle, Jaione, Solano, Cristina, Lasa, Iñigo, Toledo-Arana, Alejandro
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.12.2013; Public Library of Science (PLoS)
• Subjects: 3' Untranslated Regions - genetics; 5' Untranslated Regions - genetics; Bacteriology; Base Pairing; Biofilms; Gene expression; Gene Expression Regulation, Bacterial; Genetic aspects; Genetic research; Genetic translation; Genetics; Humans; Life Sciences; Messenger RNA; Microbial genetics; Molecular weight; Physiological aspects; Protein Biosynthesis; Proteins; Regulatory Sequences, Ribonucleic Acid - genetics; RNA, Messenger - genetics; Staphylococcal Infections - genetics; Staphylococcal Infections - pathology; Staphylococcus aureus; Staphylococcus aureus - genetics; Staphylococcus aureus - pathogenicity; France; Portugal
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1004001

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.