Systematic identification of intergenic long-noncoding RNAs in mouse retinas using full-length isoform sequencing

Area of Science:

• Molecular Biology
• Genomics
• Developmental Biology

Background:

• Long noncoding RNAs (lncRNAs) are abundant in the mouse genome and play vital roles in biological processes.
• The function of lncRNAs in the mouse retina is largely unexplored due to incomplete annotation.

Purpose of the Study:

• To comprehensively identify and annotate lncRNAs expressed in embryonic and neonatal mouse retinas.
• To investigate the functional roles of these lncRNAs in retinal development, particularly in retinal ganglion cell (RGC) differentiation.

Main Methods:

• Utilized long-reads sequencing to analyze the transcriptomes of developing mouse retinas.
• Performed differential expression analysis following the loss of key RGC differentiation regulators.
• Employed in situ hybridization to determine the expression patterns of specific lncRNAs.

Main Results:

• Identified 940 intergenic lncRNAs (lincRNAs) in developing mouse retinas, with 13% originating from unannotated loci.
• Found that lincRNA functions are closely linked to retinal physiology, with 90 lincRNAs differentially expressed after manipulation of RGC differentiation regulators.
• Discovered three lincRNAs (linc-3a, linc-3b, linc-3c) adjacent to POU-homeobox genes enriched in the ganglion cell layer, suggesting RGC-specificity.

Conclusions:

• Systematically annotated lincRNAs in embryonic and neonatal mouse retinas.
• These lincRNAs play critical regulatory roles in retinal development, including RGC differentiation.