Metabolism and Function of RNA in the Nucleus

Group leader

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We study the regulation of gene expression in yeast, both by analyzing the transcription of genes and the fate of the RNA that is produced.
In recent years it has become clear that the fraction of the genome that is transcribed is much higher than the one occupied by all known genes. Many transcription events occur in intergenic regions or overlapping in the sense and antisense orientation to canonical genes. This is what is commonly called “pervasive” transcription.

Many of the RNAs that are produced by pervasive transcription are degraded very rapidly after transcription – in fact they cannot often be detected in a wild type strain. So we often refer to this phenomenon as “hidden” or “cryptic” transcription.  
We are very interested in cryptic transcription: we study why it originates and how the RNAs that are produced (generally non-coding) are degraded.

Too much transcription can be a problem for the cell because polymerases cannot occupy simultaneously the same genomic region and they can interfere with each other. The cell has a quality control system that stops the polymerases that do not transcribe meaningful messages to prevent them from inhibiting the “right” polymerases.

We study a set of proteins that are involved in this control, called the Nrd1-Nab3-Sen1 (NNS) complex. These factors function by terminating “wrong” transcription events and by targeting the RNA produced to degradation. A sort of traffic policeman and garbage man at the same time…

At the same time or shortly after its production, the RNA has to be processed, associated to proteins and transported to the cytoplasm where it will be translated. This is a complex process that is subject to errors as many biological processes. We study the function of protein involved in the export of mRNAs from the nucleus to the cytoplasm, and we are also quite interested in how the cell deals with mistakes.
Finally, tRNAs also have “to wear a make-up” to function, in that many of the nucleotides have to be modified for allowing formation of the right structure or to be recognized correctly by other factors. We study the function of one complex of proteins that we called the EKC and that is required to modify a large class of tRNAs; but we also think that this complex might have other functions in the cell…

We work on yeast, for obvious reasons:

Selection of Publications

Mouaikel, J., Causse, S.Z., Rougemaille, M., Daubenton-Carafa, Y., Blugeon, C., Lemoine, S., Devaux, F., Darzacq, X., and Libri, D. (2013). High-Frequency Promoter Firing Links THO Complex Function to Heavy Chromatin Formation. Cell Rep 5, 1082-1094.

Porrua, O., and Libri, D. (2013). A bacterial-like mechanism for transcription termination by the Sen1p helicase in budding yeast. Nat Struct Mol Biol 20, 884-891.

Gudipati, R.K., Xu, Z., Lebreton, A., Seraphin, B., Steinmetz, L.M., Jacquier, A., and Libri, D. (2012). Extensive degradation of RNA precursors by the exosome in wild-type cells. Mol Cell 48, 409-421

Rougemaille, M., Dieppois, G., Kisseleva-Romanova, E., Gudipati, R.K., Lemoine, S., Blugeon, C., Boulay, J., Jensen, T.H., Stutz, F., Devaux, F., and Libri, D. (2008). THO/Sub2p functions to coordinate 3'-end processing with gene-nuclear pore association. Cell 135, 308-321.

Thiebaut, M., Colin, J., Neil, H., Jacquier, A., Seraphin, B., Lacroute, F., and Libri, D. (2008). Futile cycle of transcription initiation and termination modulates the response to nucleotide shortage in S. cerevisiae. Mol Cell 31, 671-682.

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