Our friend, Mayka Sanchez is applying for a PhD position within the framework of an MSCA-COFUND, funded by the EU and co’funded by La Caixa. The program is called INPhINIT and the deadline for application in 2nd February 2018.
- 3-year contract in a stimulating environment
- Complementary training
- Secondments at national and international organisations (Universities, Research Center and Private sector)
- Mentor appointed by ”la Caixa” Foundation from its network of alumni, the ”la Caixa” Fellows’ Association
- Involvement in communication and dissemination activitie
Candidates applying for a fellowship of the programme will be evaluated accordingly to their CV, letters of reference and interview.
- Candidates must have obtained a Master degree in the last 4 years
- A good command of English (B2 level required)
- It is also mandatory not to have resided in Spain more than 12 months in the last 3 years before 29 May 2018.
The E3 ubiquitin ligase TRIM25 is an antiviral factor recently discovered to bind RNA by the RNA interactome studies (Castello et al., 2012 and Kwon et al., 2013). In a recent work led by our collaborator Gracjan Michlewsky (Wellcome Centre for Cell Biology, University of Edinburgh), we dissected how this protein binds to RNA and what are the consequences of this interaction in TRIM25 function. We discovered that TRIM25 binds RNA via its PRY/SPRY domain and that the interaction with RNA enhances TRIM25 E3 ligase activity, which is necessary for its antiviral role. Using CLIP analyses we showed that TRIM25 binds G-rich sequences present in hundreds of cellular RNAs. Moreover, We discovered that TRIM25 controls the levels of a key component in the interferon response pathway, ZAP (also known as PARP13 and ZC3HAV1).
In conclusion, the E3 ligase activity of TRIM25 is controlled by RNA, breaking once more the view that proteins act on RNA and not the opposite.
RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination
Nila Roy Choudhury, Gregory Heikel, Maryia Trubitsyna, Peter Kubik, Jakub S. Nowak, Shaun Webb, Sander Granneman, Christos Spanos, Juri Rappsilber, Alfredo Castello and Gracjan Michlewski
In a recent work with Yolanda Revilla’s lab (CBMSO, Madrid) published in the Journal of Virology, we investigated the role in RNA metabolism of a protein from a complex DNA virus, called African swine fever virus (ASFV). This protein exhibits high homology with cellular decapping enzymes and thus can potentially remove the cap structure from the RNA body triggering degradation. We show that this protein interacts with viral and cellular mRNAs in infected cells. This interaction results in decreased levels of both types of transcripts, agreeing with a putative role as virus-encoded decapping activity. We propose that the degradation of RNA triggered by this protein is key to control gene expression in ASFV infected cells.
It is challenging to determine the composition of a given ribonucleoprotein. We recently approached this problem by adapting the original RNA interactome capture protocol (Castello et al., Cell 2012), to the use of specific antisense LNA probes to capture specific RNA species. We use this method to elucidate the composition of luciferase containing reporters and ribosomal RNA in vitro and in vivo. We were able to recapitulate well-established protein-RNA interactions and to discover new ones.
Specific RNP capture with antisense LNA/DNA mixmers. Rogell B, Fischer B, Rettel M, Krijgsveld J, Castello A, Hentze MW. RNA. 2017 Aug;23(8):1290-1302. doi: 10.1261/rna.060798.117. Epub 2017 May 5.
Our colleague Vicent Pelechano is looking for a postdoc in Genomics/Computational Biology to join his team at Karolinska Institutet – SciLifeLab.
The available postdoctoral position concerns developing and applying novel genomic and computational approaches to study ribosome dynamics and RNA metabolism, and its impact to cell-to-cell phenotypic heterogeneity. The candidate will focus on the computational analysis of newly developed methods to study ribosome dynamics, mRNA degradation and tRNA processing (e.g. Pelechano et al. Cell 2015). The candidate is expected to contribute to our common goal of understanding how RNA biology and post-transcriptional regulation contributes to the appearance of differences across clonal populations of cells.
The application deadline is October 2nd and you can find more information about this job here: http://pelechanolab.com/2017/06/21/postdoctoral-stipend-in-genomics-computational-biology/