Human microcephaly protein RTTN interacts with STIL and is required to build full-length centrioles

Hsin-Yi Chen, Chien-Ting Wu, Chieh-Ju C. Tang, Yi-Nan Lin, Won-Jing Wang and Tang K. Tang ()
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Hsin-Yi Chen: National Defense Medical Center
Chien-Ting Wu: Academia Sinica
Chieh-Ju C. Tang: Academia Sinica
Yi-Nan Lin: Academia Sinica
Won-Jing Wang: National Yang-Ming University
Tang K. Tang: National Defense Medical Center

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00305-0

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