New Layers of RNA Quality Control Through RNA 3’end Tailing
A study from Torben Heick Jensen’s group at the Department of Molecular Biology and Genetics, Aarhus University, uncovers a new fail-safe mechanism for RNA decay that ensures that non-productive RNA is efficiently degraded in cells that experience external stress
Due to their promiscuous premature termination of transcription, human cells produce large amounts of non-productive and non-polyadenylated (pA-) RNAs. Under normal condtions, it is vital for cells to elimate these transcripts, which is done by the RNA exosome nuclease through its Nuclear EXosome Targeting (NEXT) adaptor complex. However, NEXT activity is compromised by external stresses, such as DNA damage, identifying a need for back-up pathways.
A study published in Nature Communications and spearheaded by assistant professor Guifen Wu, now addresses this question and uncovers novel RNA fail-safe decay pathways that rely on RNA 3’end tailing; uridylation and adenylation. The research reveals that shorter pA- RNAs, following their nuclear export, are uridylated by the TUT4 and TUT7 uridylation enzymes (Figure A). Conversely, longer pA- RNAs become adenylated by the TENT2, PAPOLA and PAPOLG polyadenylation factors in the nucleus (Figure B). Despite these differences, both 3’end modifications mark such tailied RNAs for degradation in the cytoplasm. Failure to do so hampers global translation and leads to cell death, underscoring the critical role that these back-up pathways have in maintaining cellular integrity.
In an unprecedented way, the study bridges a gap between nuclear and cytoplasmic RNA decay pathways, highlighting their interplays and redundancies. Moreover, it uncovers intricate networks involving RNA tailing enzymes and export factors, which are shared with productive RNA pathways, enabling cells to deal with external stresses to maintain RNA homeostaisis.
The Research Paper
RNA 3’end tailing safeguards cells against products of pervasive transcription termination. Guifen Wu, Jérôme O. Rouvière, Manfred Schmid and Torben Heick Jensen. Nature Communications. https://doi.org/10.1038/s41467-024-54834-6
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Supplementary information
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Study type:
Research article
External funding:
The work was supported by the Novo Nordisk Foundation (ExoAdapt grant 31199 to T.H.J.) and the Danish Cancer Society (R302-A17282 to T.H.J.). G.W. was supported by a Lundbeck Foundation Postdoc grant (R347-2020-2224).
Conflict of interest:
None
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For further information, please contact
Assistant Professor Guifen Wu – wuguifen@mbg.au.dk
Professor Torben Heick Jensen – thj@mbg.au.dk
Department of Molecular Biology and Genetics, Aarhus University, Denmark