Interplay between miR-574-3p and hnRNP L regulates VEGFA mRNA translation and tumorigenesis

Nucleic Acids Research
Peng YaoPaul L Fox

Abstract

MicroRNAs (miRNAs) and heterogeneous nuclear ribonucleoproteins (hnRNPs) are families of sequence-specific, posttranscriptional modulators of gene expression. Despite extensive mechanistic and functional studies on both regulatory classes, the interactions and crosstalk between them are largely unexplored. We have reported that competition between miR-297 and hnRNP L to bind a 3΄UTR-localized CA-rich element (CARE) of VEGFA mRNA regulates its translation. Here, we show that translation of VEGFA mRNA in human myeloid cells is dictated by a bi-directional interaction between miR-574-3p, a CA-rich microRNA, and hnRNP L. In normoxia, miR-574-3p, acting as a decoy, binds cytoplasmic hnRNP L and prevents its binding to the CARE and stimulation of VEGFA mRNA translation, simultaneously permitting miR-297-mediated translational silencing. However, in hypoxia, cytoplasmic accumulation of Tyr359-phosphorylated hnRNP L sequesters miR-574-3p, overcoming its decoy activity and seed sequence-dependent gene silencing activity. Ectopically expressed miR-574-3p binds multiple RNA recognition motif (RRM) domains of hnRNP L, synergizes with miR-297, reduces VEGFA mRNA translation, and triggers apoptosis, thereby suppressing tumorigenesis. Our stu...Continue Reading

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Citations

Jul 30, 2019·EMBO Reports·Yoshihiro KawasakiTetsu Akiyama
Nov 12, 2019·Journal of Cellular and Molecular Medicine·Lei ZhangPeifeng Li
Mar 30, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Meike J SaulDieter Steinhilber
Jul 1, 2020·Journal of Clinical Medicine·Daniel P ZalewskiAnna Bogucka-Kocka
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Nov 20, 2021·The FEBS Journal·Madeleine R Smith, Guilherme Costa

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Methods Mentioned

BETA
transfection
PCR
Co-Immunoprecipitation
electrophoretic mobility shift assay
electrophoresis
chip
FCS
xenograft
RIP
SELEX

Software Mentioned

miRanda
miRDB
PITA
miRWalk
Biaevaluation
TargetScan
DIANAmT
Biacore
Ensembl Genome Browser

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