- Murn, Jernej;
- Zarnack, Kathi;
- Yang, Yawei J;
- Durak, Omer;
- Murphy, Elisabeth A;
- Cheloufi, Sihem;
- Gonzalez, Dilenny M;
- Teplova, Marianna;
- Curk, Tomaž;
- Zuber, Johannes;
- Patel, Dinshaw J;
- Ule, Jernej;
- Luscombe, Nicholas M;
- Tsai, Li-Huei;
- Walsh, Christopher A;
- Shi, Yang
Cellular morphology is an essential determinant of cellular function in all kingdoms of life, yet little is known about how cell shape is controlled. Here we describe a molecular program that controls the early morphology of neurons through a metazoan-specific zinc finger protein, Unkempt. Depletion of Unkempt in mouse embryos disrupts the shape of migrating neurons, while ectopic expression confers neuronal-like morphology to cells of different nonneuronal lineages. We found that Unkempt is a sequence-specific RNA-binding protein and identified its precise binding sites within coding regions of mRNAs linked to protein metabolism and trafficking. RNA binding is required for Unkempt-induced remodeling of cellular shape and is directly coupled to a reduced production of the encoded proteins. These findings link post-transcriptional regulation of gene expression with cellular shape and have general implications for the development and disease of multicellular organisms.