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

Sagar Mahale, Meenakshi Setia, Bharat Prajapati, Santhilal Subhash, Mukesh Pratap Yadav, Subazini Thankaswamy Kosalai, Ananya Deshpande, Jagannath Kuchlyan, Mirco Di Marco, Fredrik Westerlund, L. Marcus Wilhelmsson, Chandrasekhar Kanduri () and Meena Kanduri ()
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Sagar Mahale: University of Gothenburg
Meenakshi Setia: University of Gothenburg
Bharat Prajapati: University of Gothenburg
Santhilal Subhash: University of Gothenburg
Mukesh Pratap Yadav: University of Gothenburg
Subazini Thankaswamy Kosalai: University of Gothenburg
Ananya Deshpande: University of Gothenburg
Jagannath Kuchlyan: Chalmers University of Technology
Mirco Di Marco: University of Gothenburg
Fredrik Westerlund: Chalmers University of Technology
L. Marcus Wilhelmsson: Chalmers University of Technology
Chandrasekhar Kanduri: University of Gothenburg
Meena Kanduri: University of Gothenburg

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-32537-0

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