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

中央研究院新聞稿
揭開畸形小頭症蛋白RTTN參與細胞中心粒複製之謎-

中央研究院生物醫學研究所特聘研究員唐堂研究室與陽明大學王琬菁研究室，今年八月中旬在國際知名學術期刊「自然通訊」（Nature Communications）發表一篇重要論文，向世人呈現細胞分裂過程中的核心謎題之一：兩個小頭症蛋白RTTN與STIL如何交互作用影響中心粒的複製。這是繼2009-2013年間唐堂研究室發現3個畸型小頭症蛋白（CPAP，STIL，及CEP135）功能之後，再次重要的創新研究發現。....更多