Ph.D. Human Genetics, Yale University
Mutations in many centriolar protein-encoding genes cause primary microcephaly. Using super-resolution and electron microscopy, we find that the human microcephaly protein, RTTN, is recruited to the proximal end of the procentriole at early S phase, and is located at the inner luminal walls of centrioles. Further studies demonstrate that RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly. CRISPR/Cas9-mediated RTTN gene knockout in p53-deficient cells induce amplification of primitive procentriole bodies that lack the distal-half centriolar proteins, POC5 and POC1B. Additional analyses show that RTTN serves as an upstream effector of CEP295, which mediates the loading of POC1B and POC5 to the distal-half centrioles. Interestingly, the naturally occurring microcephaly-associated mutant, RTTN (A578P), shows a low affinity for STIL binding and blocks centriole assembly. These findings reveal that RTTN contributes to building full-length centrioles and illuminate the molecular mechanism through which the RTTN (A578P) mutation causes primary microcephaly.
Academia Sinica Press Release:
Revealing the Mysterious Role of Human Microcephaly Protein RTTN in Centriole Duplication
In a research article published in the August issue of the prestigious scientific journal Nature Communications, Dr. Tang K. Tang, a Distinguished Research Fellow at the Institute of Biomedical Sciences (IBMS), Academia Sinica, and Dr. Won-Jing Wang from National Yang-Ming University uncovers for the first time the role of a previously uncharacterized microcephaly protein RTTN during centriole duplication. ....more