A typical yeast cell contains around 40,000 molecules of messenger RNA (mRNA), whereas a typical mammalian cell more than 100,000. All these mRNAs need to be processed, exported to the nucleus to the cytoplasm, translated, and eventually degraded. This means that even in a simple eukaryotic cell - such as yeast – there are thousands of posttranscriptional events taking place simultaneously at any given time. We are interested in how these posttranscriptional events are coordinated with each other and with transcriptional control. We use the fission yeast Schizosaccharomyces pombe to study these questions, and address them with state-of-the-art genomic methods, classical and molecular genetics, and cell biological approaches. We currently concentrate on three major areas:
1. Role of RNA-binding proteins in the control of RNA decay: Together with transcription, RNA turnover determines mRNA levels. RNA decay rates are transcript-specific, and vary by up to 100-fold between genes. We are investigating how RNA-binding proteins influence decay rates, and how they coordinate the decay of groups of mRNAs.
2. Genome-wide control of translation: We recently set up for fission yeast the technique of ribosome profiling, which offers a genome-wide view of translation with single nucleotide resolution. Ribosome profiling can be used to estimate the efficiency with which any cellular RNA is translated, as well as to identify every translated region in a genome. We applied this method to S. pombe cellular development and found hundreds of translated regulatory open reading frames (uORFs, for upstream Open reading Frames), frequent translation of RNAs annotated as non-coding and widespread regulation of translational efficiency. We are now applying this approach to investigate how fission yeast cells remodel translation in response to stress conditions.
3. The fission yeast peptidome: Our ribosome profiling experiments revealed more than 900 unannotated translated regions of 20-100 codons (that is almost 20% the number of annotated coding genes). As small proteins are very difficult to predict bioinformatically and to detect experimentally, they have been generally overlooked. However, there is evidence that these proteins can have key biological function. We are using proteomic methods aimed at detecting small proteins together with reverse genetics approaches to investigate the expression and function of these novel peptides.
Lab members: Juan Mata, Caia Duncan, Sanjay Ghosh, Beth Small, George Wood
1. Cotobal C, Rodriguez-Lopez M, Duncan C, Hasan A, Yamashita A, Yamamoto M, Bahler J and Mata J (2015) Role of Ccr4-Not Complex in Heterochromatin Formation at Meiotic Genes and Subtelomeres in Fission Yeast. Epigenetics & Chromatin 8:28
2. Hasan A, Cotobal C, Duncan C and Mata J (2014) Systematic analysis of the role of RNA-binding proteins in the regulation of RNA stability. PLoS Genet 10 (11): e1004684
3. Duncan C and Mata J (2014) The translational landscape of fission yeast meiosis and sporulation. Nat Mol Struct Biol doi:10.1038/nsmb.2843
5. Mata J (2013) Genome-wide mapping of polyadenylation sites in fission yeast reveals widespread alternative polyadenylation. RNA Biology 10 (8) 1-8
7. Amorim M, Cotobal C, Duncan C and Mata J (2010) Global coordination of transcriptional control and mRNA decay during cellular differentiation. Molecular Systems Biology 6: 378
8. Mata J (2010) Systematic mapping of myosin protein - RNA networks suggests the existence of specialised protein production sites. FASEB Journal 24 (2) 479-484
9. Amorim M and Mata J (2009) Rng3p a member of the UCS family of myosin co-chaperones associates with myosin heavy chains cotranslationally. EMBO Reports 10 (2) 186–191
Prospective PhD students note that we are members of the Wellcome Trust 4-year PhD Programme in Developmental Biology, the BBSRC DTP Programme, and the four-year PhD Programme of the Department of Biochemistry.