RNA-binding protein LIN28A upregulates transcription factor HIF1α by posttranscriptional regulation via direct binding to UGAU motifs
Journal of Biological Chemistry, ISSN: 0021-9258, Vol: 299, Issue: 1, Page: 102791
2023
- 5Citations
- 8Captures
- 1Mentions
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Metrics Details
- Citations5
- Citation Indexes5
- Captures8
- Readers8
- Mentions1
- News Mentions1
- News1
Most Recent News
Tokyo Medical and Dental University (TMDU) Reports Findings in Carrier Proteins (Rna-binding Protein Lin28a Upregulates Transcription Factor Hif1 & Alpha; By Posttranscriptional Regulation Via Direct Binding To Ugau Motifs)
2023 JUL 17 (NewsRx) -- By a News Reporter-Staff News Editor at Angiogenesis Daily -- Current study results on Proteins - Carrier Proteins have been
Article Description
Hypoxia-inducible factor 1α (HIF1α) is a transcription factor that regulates angiogenesis under hypoxic conditions. To investigate the posttranscriptional regulatory mechanism of HIF1α, we performed a cell-based screening to reveal potential cis -elements and the regulatory RNA-binding proteins that act as trans -factors. We found that LIN28A promoted HIF1α protein expression independently of the downregulation of microRNA let-7, which is also directly mediated by LIN28A. Transcriptome analysis and evaluation of RNA stability using RNA-seq and SLAM-seq analyses, respectively, revealed that LIN28A upregulates HIF1A expression via mRNA stabilization. To investigate the physical association of LIN28A with HIF1A mRNA, we performed enhanced crosslinking immunoprecipitation in 293FT cells and integrally analyzed the transcriptome. We observed that LIN28A associates with HIF1A mRNA via its cis -element motif “UGAU”. The “UGAU” motifs are recognized by the cold shock domain of LIN28A, and the introduction of a loss-of-function mutation to the cold shock domain diminished the upregulatory activities performed by LIN28A. Finally, the microvessel density assay showed that the expression of LIN28A promoted angiogenesis in vivo. In conclusion, our study elucidated the role of LIN28A in enhancing the HIF1α axis at the posttranscription layer.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0021925822012340; http://dx.doi.org/10.1016/j.jbc.2022.102791; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85145583767&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/36509142; https://linkinghub.elsevier.com/retrieve/pii/S0021925822012340; https://dx.doi.org/10.1016/j.jbc.2022.102791
Elsevier BV
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