KHSRP loss increases neuronal growth and synaptic transmission and alters memory consolidation through RNA stabilization.

ABSTRACT: The KH-type splicing regulatory protein (KHSRP) is an RNA-binding protein linked to decay of mRNAs with AU-rich elements. KHSRP was previously shown to destabilize Gap43 mRNA and decrease neurite growth in cultured embryonic neurons. Here, we have tested functions of KHSRP in vivo. We find upregulation of 1460 mRNAs in neocortex of adult Khsrp^-/- mice, of which 527 bind to KHSRP with high specificity. These KHSRP targets are involved in pathways for neuronal morphology, axon guidance, neurotransmission and long-term memory. Khsrp^-/- mice show increased axon growth and dendritic spine density in vivo. Neuronal cultures from Khsrp^-/- mice show increased axon and dendrite growth and elevated KHSRP-target mRNAs, including subcellularly localized mRNAs. Furtherm

SUBMITTER: Olguin SL 

PROVIDER: S-EPMC9262970 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature