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15 novembre 2021: 1 événement

  • Séminaires Invités

    Lundi 15 novembre 14:00-15:30 - Yusuke Suenaga - Department of Molecular Carcinogenesis, Chiba Cancer Centre Research Institute, Japan

    Functional and structural characterization of de novo evolved proteins

    Résumé : New coding genes that evolved from the non-genic region are called de novo evolved genes, which encode functional proteins in taxonomically restricted species and characterize their lineage/species-specific phenotypes. In contrast to new genes that originated from pre-existing genes by duplication, de novo genes do not have known functional motifs or domains and show random-like amino acid sequences. We have previously found that NCYM, an antisense gene of the oncogene MYCN, encodes a de novo evolved gene product that stabilizes MYCN and promotes metastasis of neuroblastoma, a human pediatric tumor. Since NCYM is registered in the database as a non-coding RNA, it is possible that there are many unknown de novo evolved genes that are misclassified as non-coding RNAs. Therefore, there is a need to identify new factors that determine the coding potential.
    Recently, we discovered a mathematical structure that distinguishes non-coding RNAs from coding RNAs, which we named the PTI (potential translated island) score. This PTI score can be uniquely calculated from RNA sequences, and when calculated for all human transcripts, the relationship with coding potential was approximated by a linear function passing through the origin. Human noncoding RNAs with high coding potential were predicted to be associated with cerebral development and cancer. Furthermore, we calculated more than 3.4 million transcripts of 100 species and found that PTI is commonly associated with coding potential in cellular organisms.
    To investigate the relationship between structure and function of de novo evolved proteins, we analyzed the secondary structure of NCYM by vacuum ultraviolet circular dichroism and identified the amino acids involved in MYCN stabilization. These results suggest that the combination of structural and evolutionary analyses of de novo proteins is useful for elucidating the mechanism of new gene birth.
    Contact : Judith Peters

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