Researchers from the ULg (Franck Dequiedt’s Laboratory, GIGA-R) in collaboration with ULB, KUL and American researchers have recently published findings in the journal Nature Structural & Molecular Biology indicating that control of gene expression by mammalian transcription factors may follow a more complex scheme than previously anticipated, by regulating all the steps of the gene expression (integrating mRNA synthesis and degradation).

With this discovery, the researchers invite to review the current understanding of the eukaryotic gene regulation and this opens a wide field of new therapeutic perspectives in medical research since transcription factors are involved in the development of many diseases such as certain cancers.

Transcription factors play a fundamental role in gene regulation. However, the current model confines these proteins in the early stages of gene expression, in the synthesis of messenger RNA (transcription step). Until now, the family of ERG proteins (E-26 related gene) were considered prototypical transcription factors controlling the transcription of genes involved in fundamental processes such as proliferation, differentiation or cellular death. In a publication in Nature Structural & Molecular Biology, ULg researchers in collaboration with  ULB, KUL and US (Harvard, Dana-Farber Cancer Institute, Rockefeller University) researchers have shown that ERG-factors are involved not only in the synthesis of messenger RNA (mRNA) in the nucleus, but also during its degradation in the cytoplasm. The researchers specifically identified the molecular mechanisms associated with this new feature: the ERG factors bind to mRNA via specialized proteins (RBP: RNA-binding proteins) and then recruit the CCR4-NOT complex, a multiprotein complex ensuring deadenylation of mRNAs, the first stage of the degradation process in eukaryotes. The researchers also provided a biological context to their observations by showing that the coordinated control of the synthesis and degradation of specific mRNAs by ERG was essential to the completion of the cell mitosis process (nuclear division). These findings raise the question on the role of transcription factors since it shows that these proteins are also involved in the late stages of gene expression process. More broadly, these findings suggest that accompanying the mRNAs from their “birth” to their “death”, transcription factors play a leading role, allowing the cell to effectively coordinate all stages of gene expression.

Source: The transcription factor ERG recruits CCR4-NOT to control mRNA decay and mitotic progression.Published online on 06.06.2016 on the Nature Structural & Molecular Biology website, DOI 10.1038/nsmb.3243

https://www.nature.com/nsmb/journal/vaop/ncurrent/full/nsmb.3243.html

Authors
Xavier Rambout ^1,2, Cécile Detiffe ^1,2, Jonathan Bruyr ^1,2, Emeline Mariavelle ^1,2, Majid Cherkaoui ^1,2, Sylvain Brohée ^3,4, Pauline Demoitié ^1,2, Marielle Lebrun ^1,5, Romuald Soin ⁶, Bart Lesage ⁷, Katia Guedri ^1,2, Monique Beullens ⁷, Mathieu Bollen ⁷, Thalia A Farazi ⁸, Richard Kettmann ^1,2, Ingrid Struman ^1,9, David E Hill ^10,11, Marc Vidal ^10,11, Véronique Kruys ⁶, Nicolas Simonis ³, Jean-Claude Twizere ^1,2 & Franck Dequiedt ^1,2

1. Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULg), Liège, Belgium
2. GIGA-Molecular Biology in Diseases, ULg, Liège, Belgium
3. BiGRe, Université Libre de Bruxelles (ULB), Bruxelles, Belgium
4. Computer Science Department, ULB, Bruxelles, Belgium
5. GIGA-Inflammation, Infection & Immunity, ULg, Liège, Belgium
6. Faculté des Sciences, ULB, Gosselies, Belgium
7. Department of Cellular and Molecular Medicine, University of Leuven (KUL), Leuven, Belgium
8. Howard Huges hMedical Institute, Rockefeller University, New York, New York, USA
9. GIGA-Cancer, ULg, Liège, Belgium
10. Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA
11. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA

Frank Dequiedt / 1^st author / Université de Liège, GIGA Research – Molecular Biology of Diseases, +32 (0)4 366 92 28 / fdequiedt@ulg.ac.be

Véronique Kruys / Université libre de Bruxelles, Faculté des Sciences – Laboratoire de Biologie moléculaire du Gène, +32 (0)2 650 98 01 / Veronique.Kruys@ulb.ac.be