Ethanol- and PARP-Mediated Regulation of Ribosome-Associated Long Non-Coding RNA (lncRNA) in Pyramidal Neurons.

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Long noncoding RNAs (lncRNAs) are increasingly recognized for their diverse cellular roles, despite lacking protein-coding potential.
• Some lncRNAs associate with ribosomes, suggesting potential roles in translation or post-transcriptional regulation.
• Ethanol exposure is known to affect cellular processes, including gene expression and protein synthesis.

Purpose of the Study:

• To investigate the impact of ethanol exposure on ribosome-bound lncRNAs in CaMKIIα-expressing pyramidal neurons.
• To determine if the Poly-ADP Ribose Polymerase (PARP) inhibitor ABT-888 can modulate ethanol-induced changes in lncRNA-ribosome association.
• To identify specific lncRNA transcripts affected by ethanol and/or ABT-888 treatment.

Main Methods:

• Mice were treated with ethanol (EtOH), saline (CTL), or ethanol plus ABT-888 (EtOH+ABT) via intraperitoneal injection.
• Ribosome-bound lncRNAs were isolated from CaMKIIα-expressing pyramidal neurons using Translating Ribosome Affinity Purification (TRAP).
• Quantitative reverse transcription PCR (qRT-PCR) was used to validate changes in selected lncRNA transcripts.

Main Results:

• Ethanol altered the association of 107 lncRNA transcripts with ribosomes.
• The combination of ethanol and ABT-888 altered 60 lncRNAs, with 49 overlapping with ethanol-only effects.
• EtOH+ABT uniquely altered 11 lncRNA transcripts not affected by ethanol alone, suggesting a modulatory role for PARP inhibition.

Conclusions:

• Ethanol significantly impacts the repertoire of ribosome-bound lncRNAs in specific neuronal populations.
• The PARP inhibitor ABT-888 can mitigate some of the ethanol-induced alterations in lncRNA-ribosome interactions.
• These findings highlight a potential mechanism through which PARP inhibition might counteract ethanol's molecular effects.