Splicing regulation during meiosis

pre-mRNA processing, and more specifically splicing, is an intrinsic part in the regulation of gene expression.  As a consequence, this results in a single gene coding for multiple proteins or in the possibility to completely abolish the presence of a protein in certain developmental programs or metabolic status.  In metazoans, alterations or malfunctions of alternative splicing (AS) are implicated in disease: a large proportion of human genetic disorders result from splicing variants. Also, it has been shown that AS deregulation contributes to the development of cancer and that splicing factor genes are also frequently mutated in many types of cancer being a major contribution to the development of this disease. 

In fission yeast, we have previously shown the existence of a highly specialized splicing program that takes place only in meiosis and that is linked to the speed of the RNA polymerase when transcribing some meiotic genes.  This splicing program is essentially meant as a safe-lock mechanism to ensure the absence of some meiotic proteins during mitotic growth, which otherwise are lethal for the cells.

We have recently done a Nanopore native RNA sequencing which has revealed a myriad of new introns and new mRNA isoforms unknown so far in fission yeast (manuscript under review).  The candidate will combine these new data (data from Alba lab) with RNAseq of synchronous meiosis obtained on an Illumina platform (data from Ayte lab) and will get a full map of the AS events during meiosis.

 

References

Alves-Rodrigues, I., Ferreira, P.G., Moldón, A., Vivancos, A.P., Hidalgo, E., Guigó, R and Ayté, J. (2016) Spatiotemporal control of forkheads binding to DNA regulates the meiotic gene expression program. Cell Rep. 14:885-895.

Blevins, W.R, Ruiz-Orera, J., Messeguer, X., Blasco-Moreno, B., Villanueva-Cañas, J.L., Espinar, L., Díez, J., Carey, L.B. and Alba, M.M. (2021) Uncovering de novo gene birth in yeast using deep transcriptomics. Nat. Commun. 12:60

Hummer, S., Borao, S., Guerra-Moreno, A., Cozzuto, L. Hidalgo, E. and Ayté, J. (2021) Cross talk between the upstream exon-intron junction and Prp2 facilitates splicing of non-consensus intron.  Cell Rep. 37:109893.

Moldón, A., Malapeira, J., Gabrielli, N., Gogol, M., Gómez-Escoda, B., Ivanova, T., Seidel, C. and Ayté, J. (2008) Promoter-driven splicing regulation in fission yeast. Nature 455:997-1000.

Montañés, J.C., Huertas, M., Moro, S.G., Blevins, W.R., Carmona, M., Ayté, J., Hidalgo, E. and Albà M.M. Native RNA sequencing in fission yeast reveals frequent alternative splicing isoforms. Genome Res. (under review)

 

Skills required

R and Python programming


Supervisors: José Ayte and M. Mar Albà (IMIM, ICREA)