Cell type-specific CLIP reveals that NOVA regulates cytoskeleton interactions in motoneurons

Genome Biology

Tom Maniatis¹  Chaolin Zhang²  Shirley Xie³  Andrew J. Darnell³  Elisabeth A. Murphy³  Yuhki Saito³  Jennifer C. Darnell³  Robert B. Darnell³  Yuan Yuan³  Hemali Phatnani⁴ 

[1]Department of Biochemistry and Molecular Biophysics, Columbia University

[2]Department of Systems Biology, Columbia University

[3]Laboratory of Molecular Neuro-Oncology, The Rockefeller University

[4]New York Genome Center

关键词: Cell type-specific;    CLIP;    Motoneuron;    NOVA;    RNA;    Alternative splicing;   

DOI  :  10.1186/s13059-018-1493-2

来源: DOAJ

【 摘 要 】

Abstract Background Alternative RNA processing plays an essential role in shaping cell identity and connectivity in the central nervous system. This is believed to involve differential regulation of RNA processing in various cell types. However, in vivo study of cell type-specific post-transcriptional regulation has been a challenge. Here, we describe a sensitive and stringent method combining genetics and CLIP (crosslinking and immunoprecipitation) to globally identify regulatory interactions between NOVA and RNA in the mouse spinal cord motoneurons. Results We developed a means of undertaking motoneuron-specific CLIP to explore motoneuron-specific protein–RNA interactions relative to studies of the whole spinal cord in mouse. This allowed us to pinpoint differential RNA regulation specific to motoneurons, revealing a major role for NOVA in regulating cytoskeleton interactions in motoneurons. In particular, NOVA specifically promotes the palmitoylated isoform of the cytoskeleton protein Septin 8 in motoneurons, which enhances dendritic arborization. Conclusions Our study demonstrates that cell type-specific RNA regulation is important for fine tuning motoneuron physiology and highlights the value of defining RNA processing regulation at single cell type resolution.

【 授权许可】

Unknown