The long non-coding RNA LINC00276-202 regulates RPE differentiation through hnRNPL and β-catenin-associated signaling
Abstract
Non-coding RNAs play critical roles in regulating gene expression and diverse biological processes. While the roles of microRNAs (miRNAs/miRs) are well known, the roles of long non-coding RNAs (lncRNAs; >200 nucleotides, with little or no protein-coding potential) remain less defined. In this study, we investigated the function of lncRNAs during the differentiation of human retinal pigment epithelial (ARPE-19) cells, identifying LINC00276 as being consistently and robustly upregulated during RPE differentiation. Silencing LINC00276-202 (ENST00000418420.1) using antisense GapmeRs significantly reduced the expression of RPE differentiation-associated genes, including RPE65 , MITF , TRPM1 , and TRPM3 , whereas LINC00276-202 overexpression restored their expression levels. In silico analysis identified a shared miR-204-5p/miR-211-5p-responsive region within LINC00276-202 . Both miRNAs produced modest increases in LINC00276-202 -associated reporter activity, whereas deletion of the shared seed-recognition region attenuated this response. Importantly, despite increased accumulation of the seed-deletion transcript, the mutant construct failed to induce RPE65 expression to the extent observed with WT LINC00276-202 , indicating that sequence integrity contributes to its biological activity. RNA pull-down followed by mass spectrometry identified PURB, SART3, ANXA6, and hnRNPL as potential protein binding partners. Of these, hnRNPL was validated as a LINC00276-202 -interacting protein by RNA immunoprecipitation and immunoblotting. LINC00276-202 modulated hnRNPL protein levels, and hnRNPL contributed to LINC00276-202 -mediated regulation of β-catenin protein abundance and TCF/LEF transcriptional activity. Together, these findings identify LINC00276-202 as a novel regulator of RPE differentiation involving a miR-204/miR-211-responsive region, hnRNPL interaction, and β-catenin-associated signaling, with potential relevance to retinal degenerative disease.
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BibTeX
@article{william2026long,
title = {{The long non-coding RNA LINC00276-202 regulates RPE differentiation through hnRNPL and β-catenin-associated signaling}},
author = {Samuel William and Olga A. Postnikova and Sheetal Uppal and Tapan K. Maity and Lisa M. Jenkins and Todd Duncan and Ashish Lal and T. Michael Redmond},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-74123-0},
url = {https://www.nature.com/articles/s41598-026-74123-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The long non-coding RNA LINC00276-202 regulates RPE differentiation through hnRNPL and β-catenin-associated signaling
AU - Samuel William
AU - Olga A. Postnikova
AU - Sheetal Uppal
AU - Tapan K. Maity
AU - Lisa M. Jenkins
AU - Todd Duncan
AU - Ashish Lal
AU - T. Michael Redmond
PY - 2026
DA - 2026/10/03
JO - Scientific Reports
DO - 10.1038/s41598-026-74123-0
UR - https://www.nature.com/articles/s41598-026-74123-0
AB - Non-coding RNAs play critical roles in regulating gene expression and diverse biological processes. While the roles of microRNAs (miRNAs/miRs) are well known, the roles of long non-coding RNAs (lncRNAs; >200 nucleotides, with little or no protein-coding potential) remain less defined. In this study, we investigated the function of lncRNAs during the differentiation of human retinal pigment epithelial (ARPE-19) cells, identifying LINC00276 as being consistently and robustly upregulated during RPE differentiation. Silencing LINC00276-202 (ENST00000418420.1) using antisense GapmeRs significantly reduced the expression of RPE differentiation-associated genes, including RPE65 , MITF , TRPM1 , and TRPM3 , whereas LINC00276-202 overexpression restored their expression levels. In silico analysis identified a shared miR-204-5p/miR-211-5p-responsive region within LINC00276-202 . Both miRNAs produced modest increases in LINC00276-202 -associated reporter activity, whereas deletion of the shared seed-recognition region attenuated this response. Importantly, despite increased accumulation of the seed-deletion transcript, the mutant construct failed to induce RPE65 expression to the extent observed with WT LINC00276-202 , indicating that sequence integrity contributes to its biological activity. RNA pull-down followed by mass spectrometry identified PURB, SART3, ANXA6, and hnRNPL as potential protein binding partners. Of these, hnRNPL was validated as a LINC00276-202 -interacting protein by RNA immunoprecipitation and immunoblotting. LINC00276-202 modulated hnRNPL protein levels, and hnRNPL contributed to LINC00276-202 -mediated regulation of β-catenin protein abundance and TCF/LEF transcriptional activity. Together, these findings identify LINC00276-202 as a novel regulator of RPE differentiation involving a miR-204/miR-211-responsive region, hnRNPL interaction, and β-catenin-associated signaling, with potential relevance to retinal degenerative disease.
SN - 2045-2322
ER -