A hierarchy of Hu RNA binding proteins in developing and adult neurons

HJ Okano, RB Darnell - Journal of Neuroscience, 1997 - Soc Neuroscience
HJ Okano, RB Darnell
Journal of Neuroscience, 1997Soc Neuroscience
The Hu proteins are a group of antigens targeted in an immune-mediated
neurodegenerative disorder associated with cancer. We have cloned and characterized four
members of the Hu gene family from mouse. We find that the Hu genes encode a large
number of alternatively spliced transcripts to produce a series of related neuron-specific
RNA binding proteins. Despite this complexity, we have discerned several ordered features
of Hu expression. In the embryo, specific Hu genes are expressed in a hierarchy during …
The Hu proteins are a group of antigens targeted in an immune-mediated neurodegenerative disorder associated with cancer. We have cloned and characterized four members of the Hugene family from mouse. We find that the Hu genes encode a large number of alternatively spliced transcripts to produce a series of related neuron-specific RNA binding proteins. Despite this complexity, we have discerned several ordered features ofHu expression. In the embryo, specific Hugenes are expressed in a hierarchy during early neurogenesis. In the E16 developing cortex, mHuB is induced in very early postmitotic neurons exiting the ventricular zone, mHuDis expressed in migrating neurons of the intermediate zone, andmHuC is expressed in mature cortical plate neurons. Such a hierarchy suggests distinct functional roles for each gene in developing neurons. In the adult, all neurons express some set ofHu mRNA and protein. However, specific patterns are evident such that individual neuronal types in the hippocampus, cerebellum, olfactory cortex, neocortex, and elsewhere express from one to several Hu genes. The complexity of potential protein variants within a gene family and of different Hu family members within a neuron suggests a diverse array of function. Given the strong homologies among the Hu proteins, the Drosophilaneurogenic gene elav, and the Drosophilasplicing factor sxl, we predict that different combinations of Hu proteins determine different neuron-specific aspects of post-transcriptional RNA regulation. Our findings of specific developmental patterns of expression and the correlation between immune targeting of the Hu proteins and adult neurodegenerative disease suggest that the Hu proteins are critical in both the proper development and function of mature neurons.
Soc Neuroscience