Axonal mRNA binding of hnRNP A/B is crucial for axon targeting and maturation of olfactory sensory neurons
Nanaho Fukuda,
Tomoyuki Fukuda,
Piergiorgio Percipalle,
Kanako Oda,
Nobuyuki Takei,
Kevin Czaplinski,
Kazushige Touhara,
Yoshihiro Yoshihara,
Toshikuni Sasaoka
Affiliations
Nanaho Fukuda
Brain Research Institute, Niigata University, Niigata 951-8585, Japan; Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma 630-0192, Japan; Corresponding author
Tomoyuki Fukuda
Niigata University Graduate School of Medical and Dental Science, Niigata 951-8510, Japan
Piergiorgio Percipalle
Science Division, Biology Program, New York University Abu Dhabi, Abu Dhabi 129188, UAE; Department of Molecular Bioscience, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden
Kanako Oda
Brain Research Institute, Niigata University, Niigata 951-8585, Japan
Nobuyuki Takei
Brain Research Institute, Niigata University, Niigata 951-8585, Japan
Kevin Czaplinski
The National Institutes of Health, Bethesda, MD 20892-7768, USA
Kazushige Touhara
Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
Yoshihiro Yoshihara
RIKEN Center for Brain Science, Wako 351-0198, Japan
Toshikuni Sasaoka
Brain Research Institute, Niigata University, Niigata 951-8585, Japan
Summary: Spatiotemporal control of gene expression is important for neural development and function. Here, we show that heterogeneous nuclear ribonucleoprotein (hnRNP) A/B is highly expressed in developing olfactory sensory neurons (OSNs), and its knockout results in reduction in mature OSNs and aberrant targeting of OSN axons to the olfactory bulb. RNA immunoprecipitation analysis reveals that hnRNP A/B binds to a group of mRNAs that are highly related to axon projections and synapse assembly. Approximately 11% of the identified hnRNP A/B targets, including Pcdha and Ncam2, encode cell adhesion molecules. In Hnrnpab knockout mice, PCDHA and NCAM2 levels are significantly reduced at the axon terminals of OSNs. Furthermore, deletion of the hnRNP A/B-recognition motif in the 3′ UTR of Pcdha leads to impaired PCDHA expression at the OSN axon terminals. Therefore, we propose that hnRNP A/B facilitates OSN maturation and axon projection by regulating the local expression of its target genes at axon terminals.
