HnRNPK maintains single strand RNA through controlling double-strand RNA in mammalian cells
Artikel i vetenskaplig tidskrift, 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.

Författare

Sagar Mahale

Göteborgs universitet

Meenakshi Setia

Göteborgs universitet

Bharat Prajapati

Göteborgs universitet

Santhilal Subhash

Göteborgs universitet

Mukesh Pratap Yadav

Göteborgs universitet

Subazini Thankaswamy

Göteborgs universitet

Ananya Deshpande

Göteborgs universitet

Jagannath Kuchlyan

Chalmers, Kemi och kemiteknik, Kemi och biokemi

Mirco Di Marco

Göteborgs universitet

Fredrik Westerlund

Chalmers, Biologi och bioteknik, Kemisk biologi

Marcus Wilhelmsson

Chalmers, Kemi och kemiteknik, Kemi och biokemi

Chandrasekhar Kanduri

Göteborgs universitet

Meena Kanduri

Göteborgs universitet

Nature Communications

2041-1723 (ISSN) 20411723 (eISSN)

Vol. 13 1 4865-

Styrkeområden

Nanovetenskap och nanoteknik

Hälsa och teknik

Ämneskategorier

Cellbiologi

Utvecklingsbiologi

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

DOI

10.1038/s41467-022-32537-0

PubMed

36038571

Mer information

Senast uppdaterat

2023-10-26