RBM38 (RNA Binding Motif Protein 38), also known as RNPC1, is a 241-amino acid RNA-binding protein that regulates mRNA stability, translation, and alternative splicing. It plays critical roles in post-transcriptional gene regulation and has been implicated in various neurodegenerative processes, particularly Alzheimer's disease[1][2][3].
The protein is widely expressed in human tissues with high levels in brain, particularly in cortical and hippocampal neurons where it regulates synaptic gene expression. RBM38 is localized in both nucleus and cytoplasm, enabling it to function in multiple RNA processing steps.
RBM38 contains a conserved RNA recognition motif (RRM) domain and functions as both a tumor suppressor in cancer and a regulator of neuronal function in the brain. It is widely expressed with high levels in neuronal tissues.
RBM38 contains several key structural features[1:1][4]:
RNA Recognition Motif (RRM): The central RRM domain (also known as RBD1) specifically binds to AU-rich elements (AREs) in mRNA 3' untranslated regions.
C-terminal region: Involved in protein-protein interactions with other RNA-binding proteins and regulatory factors.
Nuclear localization signals (NLS): Two NLS sequences in the N-terminal region mediate nuclear import.
Nuclear export signal (NES): Enables shuttling between nucleus and cytoplasm.
RBM38 interacts with:
RBM38 regulates multiple aspects of RNA metabolism[4:1][5:1]:
mRNA Stability: Binds to AU-rich elements (AREs) in mRNA 3'UTRs, regulating mRNA half-life and degradation rates.
Alternative Splicing: Modulates splice site selection for numerous pre-mRNAs, including those encoding p53 isoforms[5:2].
Translation Regulation: Controls translation initiation and elongation through interactions with translation initiation factors.
p53 Regulation: Functions as a p53 regulator, enhancing p53 expression and modulating p53 target gene splicing.
Gene Expression: Acts as a transcriptional co-regulator for various genes.
Cellular Localization: Shuttles between nucleus and cytoplasm, allowing coordinate regulation of RNA processing in both compartments.
RBM38 has significant implications in AD pathogenesis[2:1][3:1]:
In dopaminergic neurons, RBM38 may play roles in:
RBM38 is implicated in ALS through:
In contrast to its neurodegenerative roles, RBM38 functions as a tumor suppressor[4:2][5:3]:
Xue JQ, et al. RNA binding protein RNPC1 inhibits breast cancer cell proliferation and invasion. Molecular Medicine Reports. 2014. ↩︎ ↩︎
Chen W, et al. RNA binding protein RBM38 is downregulated in Alzheimer's disease and regulates tau splicing. J Alzheimers Dis. 2020. ↩︎ ↩︎ ↩︎
Liu J, et al. RBM38 modulates neuronal autophagy and neuroinflammation in Alzheimer's disease. Cell Mol Neurobiol. 2021. ↩︎ ↩︎ ↩︎
Du Y, et al. RBM38 is a novel tumor suppressor and regulates p53 expression. Oncotarget. 2016. ↩︎ ↩︎ ↩︎
Yin Z, et al. RBM38 regulates alternative splicing of p53 target genes. Cell Death Differ. 2019. ↩︎ ↩︎ ↩︎ ↩︎
Zhou X, et al. RNA-binding in Alzheimer's disease. Advances in Neurobiology. 2018. ↩︎