Dr. Rosemary Kiernan - Nuclear RNA degradation complexes and their impact on gene expression and genome organization - IPBS-Toulouse, Seminar Room

Rosemary Kiernan

Institute of Human Genetics, University of Montpellier

Nuclear RNA degradation complexes and their impact on gene expression and genome organization

Pervasive transcription by RNA polymerase II (RNAPII) leads to the synthesis of many non-coding RNAs, several of which have regulatory functions. These include enhancer-associated RNAs (eRNAs) as well as promoter upstream transcripts (PROMPTs) that have been shown to influence the expression of coding genes through a variety of mechanisms. A feature of these ncRNAs is their intrinsic instability. Degradation of eRNAs and PROMPTs is carried out by the nuclear RNA exosome, together with its substrate targeting complexes, the nuclear exosome targeting complex (NEXT) and the polyA tail exosome targeting connection (PAXT). Failure to degrade these ncRNAs can induce cytotoxicity and has recently been implicated in melanoma.
Over the last several years, the Kiernan lab has used a combination of biochemical and genomic approaches to further characterize the subunit composition of nuclear exosome complexes, as well as to identify the genome-wide localization of PAXT and NEXT in human cells (1-3). Our recent data reveal the implication of nuclear RNA degradation complexes in gene regulation and enhancer-promoter interactions in 3D (4).

References

1. Contreras, X. et al. PAPgamma associates with PAXT nuclear exosome to control the abundance of PROMPT ncRNAs. Nat Commun 14, 6745 (2023).
2. Contreras, X. et al. Nuclear RNA surveillance complexes silence HIV-1 transcription. PLoS Pathog 14, e1006950 (2018).
3. Wagschal, A. et al. Microprocessor, Setx, Xrn2, and Rrp6 Co-operate to Induce Premature Termination of Transcription by RNAPII. Cell 150, 1147-1157 (2012).
4. Akkawi, C. et al. Nuclear exosome targeting complexes modulate cohesin binding and enhancer-promoter interactions in 3D. Submitted

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