RMRP mediates neuroprotection as a downstream effector of RBM3 in human neuroblastoma SH-SY5Y cells.

Authors

Shuangping Ma, Xianting Liu, Yiming Xie, Yuxuan Han, Ning Wang, Shenxue Li, Binfeng Cheng, Fei Ju, Lei Wang

Published in

Molecular genetics and genomics : MGG. Volume 301. Issue 1. Jul 28, 2026. Epub Jul 28, 2026.

Abstract

As a non-coding RNA (lncRNA), the RNA component of mitochondrial RNA processing endoribonuclease (RMRP) is implicated in ribosome biogenesis. In recent years, its role in the neurodegenerative system has been reported; however, the molecular mechanism underlying RMRP-mediated neuroprotective effects remains elusive. In the present study, we identified that RMRP expression is regulated by the RNA-binding protein RBM3. The overexpression of RBM3 significantly upregulated RMRP transcription in SH-SY5Y neural cells, whereas RBM3 knockdown led to a marked reduction in RMRP expression. Furthermore, RNA Immunoprecipitation (RIP) assays confirmed the potential interaction between RMRP and RBM3. We then investigated the functional significance of RMRP regulated by RBM3 in Parkinson's disease (PD) cell models. Exogenous overexpression of RMRP strongly attenuated cytotoxicity induced by neurotoxins rotenone (ROT) and MPP⁺ in SH-SY5Y cells, as evidenced by decreased levels of cleaved poly ADP-ribose polymerase 1 (PARP1) and enhanced cell viability. Given that RBM3 exerts robust neuroprotective effects by accelerating global protein synthesis (GPS), we hypothesized that RMRP is a key mediator of RBM3-conferred neuroprotection. Consistent with this hypothesis, RMRP overexpression enhanced the activity of eukaryotic elongation factor 2 (eEF2), a hallmark of cellular GPS. Its stimulatory effect on GPS was further validated using a puromycin incorporation assay. Collectively, our data reveal that RMRP acts as a novel effector of RBM3 in stimulating cellular GPS and conferring neuroprotective effects in SH-SY5Y cells, providing a new therapeutic target for PD.

PMID:
42517924
Bibliographic data and abstract were imported from PubMed on 28 Jul 2026.

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