PDF file: EURASNET Annual Report 2008

Participant 31 – Eduardo Eyrasa) Work performed during the periodWP6:In collaboration with Gil Ast's laboratory, Eyras' group has studied splice sites and splicing factors recognizingthese signals across the entire eukaryotic kingdom:Schwartz SH, Silva J, Burstein D, Pupko T, Eyras E, Ast G. Large-scale comparative analysis of splicing signalsand their corresponding splicing factors in eukaryotes. Genome Res. 2008 Jan;18(1):88-103.Additionally, we have searched for SR proteins across the entire eukaryotic kingdom and have determined acorrelation between the properties of the RS domain and the branch-site signals, which points to a possible originof regulated splicing. This work was presented at a Workshop in Milan (4.H) and at a visit at F. Allain´s lab (4.I).This was also presented at the 1 st EURASNET conference in Krakow (2B,2C,4B-4D) and is published in Trendsin Genetics:Plass M, Agirre E, Reyes D, Camara F, Eyras E. Co-evolution of the branch site and SR proteins in eukaryotes.Trends Genet. 2008 Dec;24(12):590-4.This work on the evolution of alternative splicing has allowed us to participate in the Annual Meeting of theSociety of Molecular Biology and Evolution (2A) and to interact with experts in this area (4F).WP13:Mariano Allo from A. Kornblihtt's lab has visited Eyras' lab for 2 weeks (4.G) to start a collaborative project onthe regulation of splicing by small RNAs. Mariano's experiments show that small interference RNAs (siRNAs) cantarget sequences located close to an alternative exon are able to regulate its alternative pre-mRNA splicing inmammalian cells. The PhD student Eneritz Agirre (1.A, 3A) is performing a genome-wide analysis in order to findpossible micro-RNA targets that are likely regulated by the same mechanism.WP7:In collaboration with C. Smith group we are working on a new method for predicting Branch Sites (Bss) in orderto characterize the splicing of introns with distant BSs. These are related with long AG exclusion zones (Agez).We have analyzed long AGez across 7 mammalian species and found specific gene families that are particularlyenriched for long AGez. We also found that there is a constant rate of net gain of long AGez across mammals.This was work was presented as a poster in the IFM Eurasnet meeting at Valencia (2.E). We are working on a newprobabilistic method to predict dBSs based on previous work from Eyras' lab, which was presented at the AS-SIG2008 meeting at ISMB2008 (4.J), Toronto, and which has been published recently (2D)Corvelo A, Eyras E. Exon creation and establishment in human genes. Genome Biol. 2008;9(9):R141.WP8:We are analyzing CLIP-Seq data (Master student Juan-Ramon Gozalez-Vallinas, 1.B) with the aim to develop aprobabilistic method to study the binding strength of splicing-factors to mRNA substrates and also to determine anRNA-code of interaction for these factors.WP16:E. Eyras is coorganizer of an Interdisciplinary Focus Meeting of the EURASNET network with title “Decipheringthe splicing code: the role of protein-RNA interactions", which will take place as the Special Interest Groupmeeting on Alternative Splicing of the ISMB2009 conference in Stockholm, Sweden, the 27 and 28 of June. Theprogram and other details of this meeting are hosted at a web site (www.alternative-splicing.org) (3.D), which ismanaged by E. Eyras.b) Major cost items with justificationParticipant 1B Type of expenditure Budget total costspersonnel 14.029,10Consumables / training 0Other 4.777,98equipment 828,64Travel 4.014,28= total direct costs 23.650192