Hnrpab regulates neural development and neuron cell survival after glutamate stimulation

Abstract

The molecular mechanisms that govern the timing and fate of neural stem-cell differentiation toward the distinct neural lineages of the nervous system are not well defined. The contribution of post-transcriptional regulation of gene expression to neural stem-cell maintenance and differentiation, in particular, remains inadequately characterized. The RNA-binding protein Hnrpab is highly expressed in developing nervous tissue and in neurogenic regions of the adult brain, but its role in neural development and function is unknown. We raised a mouse that lacks Hnrpab expression to define what role, if any, Hnrpab plays during mouse neural development. We performed a genome-wide quantitative analysis of protein expression within the hippocampus of newborn mice to demonstrate significantly altered gene expression in mice lacking Hnrpab relative to Hnrpab-expressing littermates. The proteins affected suggested an altered pattern of neural development and also unexpectedly indicated altered glutamate signaling. We demonstrate that Hnrpab -/-neural stem and progenitor cells undergo altered differentiation patterns in culture, and mature Hnrpab -/-neurons demonstrate increased sensitivity to glutamate-induced excitotoxicity. We also demonstrate that Hnrpab nucleocytoplasmic distribution in primary neurons is regulated by developmental stage.

The Transacting Factor CBF-A/Hnrnpab Binds to the A2RE/RTS Element of Protamine 2 mRNA and Contributes to Its Translational Regulation during Mouse Spermatogenesis

“…Analysis of the cytoplasmic fractions showed a much larger variation in the p37 to p42 ratios (Figure 1B). p37 is more abundant than p42 in the cytoplasmic fractions in brain, consistent with a previous study [31], and we observed the same pattern in both ovary and testis (Figure 1B), suggesting a possible common function of CBF-A among these three tissues.…”

“…In order to examine whether CBF-A plays a role in the Prm2 mRNA regulation in vivo, we analyzed the Prm2 mRNA and PRM2 expression in the testis of the recently established CBF-A knockout mouse, referred to as Hnrnpab −/− [31]. Using the SAK22 and ICCI antibodies, we confirmed that neither p37 nor p42 are present in the testes of homozygous mice (Figures 7A–B; Figure S5).…”

40LoVe and Samba Are Involved in Xenopus Neural Development and Functionally Distinct from hnRNP AB

“…However, since both Samba and hnRNP AB have been reported to play a role in neural development, we performed functional assays focused on neural development [11], [17].…”

RNA detection in situ with FISH-STICs

“…The cells were then washed in PBS with 0.1 M glycine (PBSG) for 10 min and then permeabilized and stored in 80% methanol overnight at −20°C. Neuronal cultures were maintained according to the procedure described previously (Sinnamon et al 2012). Briefly, E18 timed pregnant mice were sacrificed using CO 2 in accordance with IACUC protocols.…”