Cell type-specific HITS-CLIP reveals differential RNA processing in motor neurons. Mus musculus strain:C57BL/6 | breed:Jackson

Alternative RNA processing plays an essential role in shaping cell identity and connectivity in the central nervous system (CNS). The vast cellular diversity in the CNS implicates differential regulation of RNA processing in various cell types. However, in vivo study of transcriptome-wide RNA regulation in a cell-type specific manner has been a challenge given the cellular and molecular complexity of the CNS. Here, we generated bacterial artificial chromosome (BAC)-transgenic mice expressing motoneuron-specific tagged Nova2 protein, and used cross-linking immunoprecipitation (CLIP) to study RNA regulation specifically in spinal cord motor neurons. For a subset of motor neuron messenger RNAs (mRNAs), we identified differential RNA regulation otherwise obscured in whole spinal cord CLIP, highlighting the value of defining RNA processing regulation at single cell type resolution.