PIN1 transcript variant 2 acts as a long non-coding RNA that controls the HIF-1-driven hypoxic response

Yong Joon Choi, Iljin Kim, Jae Eun Lee, Jong-Wan Park

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The transcription factor HIF-1 induces the expression of genes that are essential for cell survival and oxygen homeostasis in hypoxic conditions. The prolyl isomerase Pin1 plays a role in the regulation of HIF-1α. However, the mechanism by which Pin1 controls HIF-1α remains controversial. Surprisingly, we here show that a PIN1 transcript downregulates HIF-1α as a long non-coding RNA. Pin1-silencing siRNAs augmented the hypoxia-induced expression of HIF-1α, thereby upregulating the expression of HIF-1 target genes. However, the overexpression of Pin1 protein did not inhibit the hypoxic expression of HIF-1α. Pin1 restoration in Pin1-depleted cells also failed to reverse the induction of HIF-1α by Pin1 knockdown. Unexpectedly, HIF-1α was found to be induced by both siRNAs for PIN1 transcript variants 1/2 and that for PIN1 transcript variants 2/3, indicating that the PIN1 transcript variant 2 (PIN1-v2) is responsible for HIF-1α induction. Mechanistically, PIN1-v2, which is classified as a long non-coding RNA due to early termination of translation, was evaluated to inhibit the transcription of HIF1A gene. In conclusion, PIN1-v2 may function in balancing the HIF-1-driven gene expression under hypoxia.

Original languageEnglish
Article number10599
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2019

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Long Noncoding RNA
Peptidylprolyl Isomerase
Genes
Cell Survival
Homeostasis
Transcription Factors
Down-Regulation
Oxygen
Gene Expression
Proteins
Hypoxia

Cite this

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title = "PIN1 transcript variant 2 acts as a long non-coding RNA that controls the HIF-1-driven hypoxic response",
abstract = "The transcription factor HIF-1 induces the expression of genes that are essential for cell survival and oxygen homeostasis in hypoxic conditions. The prolyl isomerase Pin1 plays a role in the regulation of HIF-1α. However, the mechanism by which Pin1 controls HIF-1α remains controversial. Surprisingly, we here show that a PIN1 transcript downregulates HIF-1α as a long non-coding RNA. Pin1-silencing siRNAs augmented the hypoxia-induced expression of HIF-1α, thereby upregulating the expression of HIF-1 target genes. However, the overexpression of Pin1 protein did not inhibit the hypoxic expression of HIF-1α. Pin1 restoration in Pin1-depleted cells also failed to reverse the induction of HIF-1α by Pin1 knockdown. Unexpectedly, HIF-1α was found to be induced by both siRNAs for PIN1 transcript variants 1/2 and that for PIN1 transcript variants 2/3, indicating that the PIN1 transcript variant 2 (PIN1-v2) is responsible for HIF-1α induction. Mechanistically, PIN1-v2, which is classified as a long non-coding RNA due to early termination of translation, was evaluated to inhibit the transcription of HIF1A gene. In conclusion, PIN1-v2 may function in balancing the HIF-1-driven gene expression under hypoxia.",
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PIN1 transcript variant 2 acts as a long non-coding RNA that controls the HIF-1-driven hypoxic response. / Choi, Yong Joon; Kim, Iljin; Lee, Jae Eun; Park, Jong-Wan.

In: Scientific Reports, Vol. 9, No. 1, 10599, 01.12.2019.

Research output: Contribution to journalArticleResearchpeer-review

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