WITHDRAWN: hnRNPM Deficiency Deteriorates Cognitive Function by Decreasing Synaptic Proteins

Abstract

Heterogeneous nuclear ribonucleoproteins (hnRNPs), a wide sub-family within the diverse RNA-binding proteins family, contribute to multiple aspects of nucleic acid metabolism including alternative splicing, mRNA stabilization, transcriptional, posttranscriptional and translational regulation. In this study, we report that alteration to the endogenous level of Heterogeneous nuclear ribonucleoprotein M (hnRNPM) in pyramidal cells of the CA1 hippocampal region of young wildtype mice brain leads to cognitive dysfunction. We further show that deficit to hnRNPM level impedes synaptic transmission while affecting the expression levels of pre- and post-synaptic markers following its binding to the 3´UTR of synaptophysin (SYP) and Postsynaptic Density Protein 95 (PSD95). In addition, we gathered that knockdown of hnRNPM affects the expression level of NeuN (Rbfox3), a protein essential for hippocampal neurogenesis and synaptogenesis. These further suggest that diminished level of hnRNPM could lead to synaptic dysfunction or deficits in neurogenesis and impaired cognitive functions as reported in NeuN homozygous knockout mice. Furthermore, we then show that hnRNPM binds directly and significantly to the 3´UTR of NeuN, synaptophysin and PSD95 to stabilize their mRNA. Our findings present a novel insight into the regulatory role of hnRNPM in synaptic transmission and cognitive functions.