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Accueil > Départements > Biologie des Génomes > Equipes rattachées à la direction de l’I2BC > Maria COSTA : Structure, Fonction et Evolution des Retrotransposons Bactériens

Publications de l’équipe


  • M. Meyer, H. Walbott, V. Olieric, J. Kondo, M. Costa, et B. Masquida, « Conformational adaptation of UNCG loops upon crowding », RNA (New York, N.Y.), août 2019.
    Résumé : If the A-form helix is the major structural motif found in RNA, the loops that cap them constitute the second most important family of motifs. Among those, two are over-represented, the GNRA and the UNCG tetraloops. Although one might think that these consensus sequences imply distinct and specific architectures, such is not the case. Recent surveys of RNA structures deposited in the PDB show that GNRA and UNCG tetraloops can adopt tertiary folds that are very different from their canonical conformations, characterized by the presence of a U-turn of a Z-turn, respectively. In this study, crystallographic data derived from both a Lariat-Capping (LC) ribozyme and a group II intron ribozyme reveal that a given UUCG tetraloop can adopt a distinct fold depending on its direct structural environment. Specifically, when the crystal packing applies relaxed constraints on the loop, the canonical Z-turn conformation is observed. In contrast, a highly-packed environment induces "squashing" of the tetraloop by distorting its sugar-phosphate backbone in a specific way that expels the first and fourth nucleobases out of the loop, and falls in van der Waals distance of the last base pair of the helix, taking the place of the pair formed between the first and fourth residues in Z-turn loops. Importantly, the biological relevance of our observations is supported by the presence of similarly deformed loops in the highly-packed environment of the ribosome and in a complex between a dsRNA and a yeast RNase III. The finding that Z-turn loops can change conformation under higher molecular packing suggests that, in addition to their early demonstrated role in stabilizing RNA folding, they may also contribute to the three-dimensional structure of RNA by mediating tertiary interactions with distal residues.
    Mots-clés : DBG, group II intron, Lariat-Capping ribozyme, RIBOZYMO, UNCG tetraloop, Z-turn loop.


  • M. Costa, H. Walbott, D. Monachello, E. Westhof, et F. Michel, « Crystal structures of a group II intron lariat primed for reverse splicing », Science (New York, N.Y.), vol. 354, nᵒ 6316, déc. 2016.
    Résumé : The 2'-5' branch of nuclear premessenger introns is believed to have been inherited from self-splicing group II introns, which are retrotransposons of bacterial origin. Our crystal structures at 3.4 and 3.5 angstrom of an excised group II intron in branched ("lariat") form show that the 2'-5' branch organizes a network of active-site tertiary interactions that position the intron terminal 3'-hydroxyl group into a configuration poised to initiate reverse splicing, the first step in retrotransposition. Moreover, the branchpoint and flanking helices must undergo a base-pairing switch after branch formation. A group II-based model of the active site of the nuclear splicing machinery (the spliceosome) is proposed. The crucial role of the lariat conformation in active-site assembly and catalysis explains its prevalence in modern splicing.
    Mots-clés : DBG, RIBOZYMO, RNASTR.

  • D. Monachello, F. Michel, et M. Costa, « Activating the branch-forming splicing pathway by reengineering the ribozyme component of a natural group II intron », RNA (New York, N.Y.), vol. 22, nᵒ 3, p. 443-455, mars 2016.
    Résumé : When assayed in vitro, group IIC self-splicing introns, which target bacterial Rho-independent transcription terminators, generally fail to yield branched products during splicing despite their possessing a seemingly normal branchpoint. Starting with intron O.i.I1 from Oceanobacillus iheyensis, whose crystallographically determined structure lacks branchpoint-containing domain VI, we attempted to determine what makes this intron unfit for in vitro branch formation. A major factor was found to be the length of the helix at the base of domain VI: 4 base pairs (bp) are required for efficient branching, even though a majority of group IIC introns have a 3-bp helix. Equally important for lariat formation is the removal of interactions between ribozyme domains II and VI, which are specific to the second step of splicing. Conversely, mismatching of domain VI and its proposed first-step receptor in subdomain IC1 was found to be detrimental; these data suggest that the intron-encoded protein may promote branch formation partly by modulating the equilibrium between conformations specific to the first and second steps of splicing. As a practical application, we show that by making just two changes to the O.i.I1 ribozyme, it is possible to generate sufficient amounts of lariat intron for the latter to be purified and used in kinetic assays in which folding and reaction are uncoupled.
    Mots-clés : Bacillus, DBG, group II intron, Introns, lariat intron, linear intron, Phylogeny, RIBOZYMO, RNA Splicing, RNA, Catalytic, self-splicing.
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Publications Principales avant 2015

- Costa M*, Monachello D (2014) Probing RNA folding by hydroxyl radical footprinting.
Methods Mol Biol. 1086:119-42.

- Li CF, Costa M, Michel F (2011) Linking the branchpoint helix to a newly found receptor allows lariat formation by a group II intron. EMBO J . 30(15):3040-51.

- Li CF, Costa M, Bassi G, Lai YK, Michel F (2011) Recurrent insertion of 5’-terminal nucleotides and loss of the branchpoint motif in lineages of group II introns inserted in mitochondrial preribosomal RNAs. RNA . 17:1321-35.

- Mullineux ST, Costa M, Bassi GS, Michel F, Hausner G (2010) A group II intron encodes a functional LAGLIDADG homing endonuclease and self-splices under moderate temperature and ionic conditions. RNA . 16:1818-31.

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