Axonal mRNA binding of hnRNP A/B is crucial for axon targeting and maturation of olfactory sensory neurons

Cell Rep. 2023 Apr 20;42(5):112398. doi: 10.1016/j.celrep.2023.112398. Online ahead of print.

Fukuda N1, Fukuda T2, Percipalle P3, Oda K4, Takei N4, Czaplinski K5, Touhara K6, Yoshihara Y7, Sasaoka T4.

1Brain Research Institute, Niigata University; Graduate School of Biological Sciences, Nara Institute of Science and Technology

2Niigata University Graduate School of Medical and Dental Science

3Science Division, Biology Program, New York University Abu Dhabi; Department of Molecular Bioscience, The Wenner-Gren Institute, Stockholm University

4Brain Research Institute, Niigata University

5The National Institutes of Health

6Graduate School of Agricultural and Life Sciences, The University of Tokyo

7RIKEN Center for Brain Science

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.

*Reprinted under a CC BY NC ND 4.0 license.


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