Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat.

Area of Science:

• Genomics
• Molecular Biology
• Neuroscience

Background:

• Most of the mammalian genome is transcribed, producing diverse RNA molecules including long non-coding RNAs (lncRNAs).
• Nuclear-enriched ncRNAs often have unknown functions, though some antisense lncRNAs regulate gene expression via sense-antisense pairing.
• Ubiquitin carboxy-terminal hydrolase L1 (Uchl1) is crucial for brain function and implicated in neurodegenerative diseases.

Purpose of the Study:

• To identify and characterize novel nuclear-enriched lncRNAs.
• To investigate the function of a newly identified lncRNA antisense to the Uchl1 gene.
• To elucidate the regulatory mechanisms of Uchl1 protein synthesis.

Main Methods:

• Identification of nuclear-enriched lncRNAs using transcriptomic analysis.
• Experimental validation of antisense Uchl1 RNA's interaction with Uchl1 mRNA.
• Assessment of Uchl1 protein levels under various conditions, including mTORC1 inhibition.
• Analysis of RNA localization and polysome association.

Main Results:

• A novel nuclear-enriched lncRNA, antisense Uchl1, was identified.
• Antisense Uchl1 enhances Uchl1 protein synthesis post-transcriptionally.
• Its activity relies on a 5' overlapping sequence and an embedded SINEB2 element.
• Rapamycin-induced mTORC1 inhibition increases UCHL1 protein by promoting antisense Uchl1 export to the cytoplasm, facilitating translation.

Conclusions:

• A new class of functional lncRNAs, antisense Uchl1, has been identified.
• Antisense Uchl1 regulates Uchl1 protein synthesis at the post-transcriptional level.
• Stress signaling pathways modulate antisense Uchl1 activity, impacting UCHL1 translation and revealing a new gene expression control mechanism.