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HnRNPK maintains single strand RNA through controlling double-strand RNA in mammalian cells.

Sagar MahaleMeenakshi SetiaBharat PrajapatiSanthilal SubhashMukesh Pratap YadavSubazini Thankaswamy KosalaiAnanya DeshpandeJagannath KuchlyanMirco Di MarcoFredrik WesterlundL Marcus WilhelmssonChandrasekhar KanduriMeena Kanduri
Published in: Nature communications (2022)
Although antisense transcription is a widespread event in the mammalian genome, double-stranded RNA (dsRNA) formation between sense and antisense transcripts is very rare and mechanisms that control dsRNA remain unknown. By characterizing the FGF-2 regulated transcriptome in normal and cancer cells, we identified sense and antisense transcripts IER3 and IER3-AS1 that play a critical role in FGF-2 controlled oncogenic pathways. We show that IER3 and IER3-AS1 regulate each other's transcription through HnRNPK-mediated post-transcriptional regulation. HnRNPK controls the mRNA stability and colocalization of IER3 and IER3-AS1. HnRNPK interaction with IER3 and IER3-AS1 determines their oncogenic functions by maintaining them in a single-stranded form. hnRNPK depletion neutralizes their oncogenic functions through promoting dsRNA formation and cytoplasmic accumulation. Intriguingly, hnRNPK loss-of-function and gain-of-function experiments reveal its role in maintaining global single- and double-stranded RNA. Thus, our data unveil the critical role of HnRNPK in maintaining single-stranded RNAs and their physiological functions by blocking RNA-RNA interactions.
Keyphrases
  • nucleic acid
  • transcription factor
  • binding protein
  • genome wide
  • gene expression
  • single cell
  • machine learning
  • deep learning
  • artificial intelligence
  • big data
  • data analysis