Cytoplasmic long noncoding RNAs are differentially regulated and translated during human neuronal differentiation

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Long noncoding RNAs (lncRNAs) are abundant in the human nervous system.
• The cytoplasmic functions and translation of neuronal lncRNAs are largely unknown.
• Neuronal differentiation involves complex regulatory mechanisms.

Purpose of the Study:

• To investigate the interaction of cytoplasmic lncRNAs with translation machinery during neuronal differentiation.
• To identify functional consequences of lncRNA translation in human neurons.
• To explore the role of specific translated lncRNAs in neuronal development and disease.

Main Methods:

• Utilized Poly-Ribo-Seq to profile lncRNA-ribosome interactions.
• Analyzed human SH-SY5Y cells undergoing neuronal differentiation.
• Performed bioinformatic analysis of publicly available datasets for expression and cancer association.

Main Results:

• Identified 237 upregulated cytoplasmic lncRNAs during neuronal differentiation, with 58%-70% associated with polysomes.
• Discovered 45 actively translated small open reading frames (smORFs) within lncRNAs, 17 specific to differentiation.
• Found conserved, dynamically expressed, and cancer-associated translated lncRNAs, including LINC01116, which promotes neurite outgrowth.

Conclusions:

• Cytoplasmic lncRNAs serve as a source of novel peptides through translation.
• Translated lncRNAs, such as LINC01116, play functional roles in neuronal differentiation and neurite development.
• These findings link lncRNA translation to neuronal function, human brain development, and central nervous system cancers.