LncRNA fate (by D.FORETEK, MSC grant)

LncRNA fate in cytoplasm and role in multiple myeloma.

After transcription and processing, long noncoding (lnc) RNAs can be retained in nucleus, where they play multiple epigenetically relevant function or be exported to cytoplasm. Cytoplasmic lncRNAs can serve as sponges for miRNAs, regulate mRNA stability, translation or bind to proteins modulating their enzymatic activity. Emerging evidence also suggest that even though they were thought to be a class of non-coding transcripts, some of them encode peptides that could have a regulatory role. Thus, it is crucial to understand better the enzymes involved in regulation of cytoplasmic lncRNA levels. Using the auxin inducible degron system, we obtained data for two major exonucleases involved in RNA decay showing an accumulation of lncRNAs in cytoplasm. Our results indicate a low conservation of XRN1 role in lncRNA stability in human cells and major role of DIS3 and 3’-5’ exonucleolytic pathway. We are further interested in determination of function of DIS3 regulated short lived transcripts in production of regulatory peptides. This is of special relevance and interest in context of multiple myeloma patients where mutations in DIS3 are linked to worse prognosis.

Our collaborators:

# Olivier Namy (I2BC, Gif sur Yvette, France)

#Steven West (Exeter Living Systems Institute, Exeter, UK)

#Dominique Weil (UPMC, Paris, France)

# Claudia Haferlach (MLL Münchner Leukämielabor GmbH, Munich, Germany)

 

Funding:

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 795109.