5 years ago

The hnRNP RALY regulates transcription and cell proliferation by modulating the expression of specific factors, including the proliferation-marker E2F1.

Macchi, Singh, Gasperini, Padgett, Tebaldi, Rossi, Cornella
The heterogeneous nuclear ribonucleoproteins (hnRNPs) form a large family of RNA-binding proteins that exert numerous functions in RNA metabolism. RALY is a member of the hnRNP family that binds poly-U rich elements within several RNAs and regulates the expression of specific transcripts. RALY is upregulated in different types of cancer, and its downregulation impairs cell cycle progression. However, RALY's role in regulating RNA levels remains elusive. Here, we show that numerous genes coding for factors involved in transcription and cell cycle regulation exhibit an altered expression in RALY-downregulated HeLa cells, consequently causing impairments in transcription, cell proliferation and cell cycle progression. Interestingly, by comparing the list of RALY targets with the list of genes affected by RALY downregulation, we found an enrichment of RALY mRNA targets in the downregulated genes upon RALY silencing. The affected genes include the E2F transcription factor family. Given its role as proliferation-promoting transcription factor, we focused on E2F1. We demonstrate that E2F1 mRNA stability and E2F1 protein levels are reduced in cells lacking RALY expression. Finally, we also show that RALY interacts with transcriptionally active chromatin in both an RNA-dependent and -independent manner, and that this association is abolished in absence of active transcription. Taken together, our results highlight the importance of RALY as an indirect regulator of transcription and cell cycle trough the regulation of specific mRNA targets, and strengthen the possibility of a direct gene expression regulation exerted by RALY.

Publisher URL: http://doi.org/10.1074/jbc.M117.795591

DOI: 10.1074/jbc.M117.795591

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