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http://purl.uniprot.org/citations/34787639http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Purpose

Retinal pigment epithelium (RPE) cell proliferation is precisely regulated to maintain retinal homoeostasis. Microphthalmia-associated transcription factor (MITF), a critical transcription factor in RPE cells, has two alternatively spliced isoforms: (+)MITF and (-)MITF. Previous work has shown that (-)MITF but not (+)MITF inhibits RPE cell proliferation. This study aims to investigate the role of long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) in regulating MITF splicing and hence proliferation of RPE cells.

Methods

Mouse RPE, primary cultured mouse RPE cells, and different proliferative human embryonic stem cell (hESC)-RPE cells were used to evaluate the expression of (+)MITF, (-)MITF, and NEAT1 by reverse-transcription PCR (RT-PCR) or quantitative RT-PCR. NEAT1 was knocked down using specific small interfering RNAs (siRNAs). Splicing factor proline- and glutamine-rich (SFPQ) was overexpressed with the use of lentivirus infection. Cell proliferation was analyzed by cell number counting and Ki67 immunostaining. RNA immunoprecipitation (RIP) was used to analyze the co-binding between the SFPQ and MITF or NEAT1.

Results

NEAT1 was highly expressed in proliferative RPE cells, which had low expression of (-)MITF. Knockdown of NEAT1 in RPE cells switched the MITF splicing pattern to produce higher levels of (-)MITF and inhibited cell proliferation. Mechanistically, NEAT1 recruited SFPQ to bind directly with MITF mRNA to regulate its alternative splicing. Overexpression of SFPQ in ARPE-19 cells enhanced the binding enrichment of SFPQ to MITF and increased the splicing efficiency of (+)MITF. The binding affinity between SFPQ and MITF was decreased after NEAT1 knockdown.

Conclusions

NEAT1 acts as a scaffold to recruit SFPQ to MITF mRNA and promote its binding affinity, which plays an important role in regulating the alternative splicing of MITF and RPE cell proliferation."xsd:string
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http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/author"Chang L."xsd:string
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/author"Hou L."xsd:string
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/author"He J."xsd:string
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/author"Jiang Y."xsd:string
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/author"Hu X."xsd:string
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/author"Li F."xsd:string
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/author"Ma X."xsd:string
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/author"Yang J."xsd:string
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/author"Wei D."xsd:string
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/author"Jiang M."xsd:string
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/author"Hejtmancik J.F."xsd:string
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/name"Invest Ophthalmol Vis Sci"xsd:string
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/pages"18"xsd:string
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/title"LncRNA NEAT1 Recruits SFPQ to Regulate MITF Splicing and Control RPE Cell Proliferation."xsd:string
http://purl.uniprot.org/citations/34787639http://purl.uniprot.org/core/volume"62"xsd:string
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