Human-specific Alternative Splicing, Brain
Development, and Ciliopathies

2023 Scientific Innovations Award
Chaolin Zhang, Ph.D.
Columbia University

Like movie frames needing to be edited to tell an engaging story, pieces of genetic information
stored in DNA for each gene need to be sliced and rejoined, through a process called “splicing”,
to produce the RNA “transcripts” that dictate protein translation. RNA splicing patterns can
diverge across different species during evolution, and human-specific splicing patterns may
contribute to why human is human. Not only does this include our unparalleled cognitive
capacities and problem-solving skills, but also why humans are susceptible for a range of
diseases, including certain neural developmental disorders and dementia. Dr. Zhang’s lab recently found
human-specific splicing patterns frequently occur in a group of genes related to a cell organelle
named cilium. Cilia are tiny, hair-like structures that protrude from the surface of nearly all
mammalian cells to sense their environments and participate in cell-cell communications, which
is critical for development of human organs, including the brain. Disruptions of cilia function are
known to cause a number of severe, multi-systemic diseases collectively known as ciliopathies.
In this project, Dr. Zhang aims to understand the function of these human-specific splicing events, how
they might contribute to human-specific brain development, and how mutations disrupting such
events might be linked to ciliopathies, such as Joubert and Merckel syndromes currently with
tremendous unmet medical needs.

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