Riboregulation: when RNA controls protein function

It is established that interactions of proteins with RNA play a crucial role at regulating RNA fate. However, a recent work led by the Hentze lab at EMBL has discovered that the reverse relationship is also possible. In other words, proteins can be regulated by RNA. We refer to this phenomenon as ‘riboregulation’.

This study shows that the RNA vault 1-1 (vtRNA1-1) interacts and regulates the protein p62, which is a key component of the autophagy machinery. As its name suggests, autophagy is a process by which a cell ‘eats itself’ to recycle its unnecessary or dysfunctional components. Interaction of vtRNA1-1 with p62 inhibits autophagy and this regulatory circuit exists in both human and mouse cells.

Importantly, the amount of vtRNA1-1 inside a cell varies according to the cell’s nutritional status. When is deprived of amino acids, vtRNA1-1 is reduced to enhance autophagy that will refill the pool of amino acids from unnecessary proteins to cover the cell needs.

This study raises the question of how common ‘riboregulation’ is and which processes are controlled by RNA. We hope to find the answer to these important questions in the years to come.

Original publication

The Small Non-coding Vault RNA1-1 Acts as a Riboregulator of Autophagy. Horos R, Büscher M, Kleinendorst R, Alleaume AM, Tarafder AK, Schwarzl T, Dziuba D, Tischer C, Zielonka EM, Adak A, Castello A, Huber W, Sachse C, Hentze MW. Cell. 2019 Feb 21;176(5):1054-1067.e12. doi: 10.1016/j.cell.2019.01.030. Epub 2019 Feb 14.PMID: 30773316

Developing a successful part II project

Jess and Morgan have worked in their part II projects for near six months in the Castello lab. They have studied different aspects of HIV biology by using cutting edge RNA biology, virology, molecular biology and microscopy techniques. Morgan has developed a new approach to elucidate the composition of the HIV ribonucleoproteins. Jess has assessed whether cellular RNA-binding proteins are incorporated into HIV particles. We hope they enjoyed working in the lab and wish them all the best for the coming scientific challenges.

Princeton student visit the Castello lab

Leslie worked in the Castello lab for five months as part of her degree in Princeton. She was interested in the understanding the role of a family of tumour suppressors recently classified as RNA-binding proteins by RNA interactome studies.

“Applying for this semester-long research opportunity at Oxford is one of the best decisions I have made at Princeton!  I am constantly intellectually stimulated and challenged by my research project and my PI’s thoughtful feedback – said Leslie-.  In my lab’s supportive environment,  I have come to really appreciate microscopy, beautiful silver staining/Western blot gels, the satisfying popping sound in the homogenizing process of my RNA interactome capture whole cell lysates, and so much more!  Would definitely consider coming back for grad school!”

Join us as a postdoctoral associate

Postdoctoral Research Associate in ‘Elucidating The Role of Cellular RNA-binding Proteins in Virus Infection’

We are seeking to appoint a Postdoctoral Research Associate to elucidate, on a proteome-wide scale, the cellular players interplaying with viral RNA in infected cells. This project involves the development of new high-throughput methods to study protein-RNA interactions using the latest proteomics and RNA sequencing platforms. Moreover, we will employ state-of-the-art virology and RNA biology techniques to characterise these interactions in depth.

Applicants should possess a PhD/DPhil, or be near completion of a PhD/DPhil, in biochemistry, molecular biology or related discipline and should have experience in molecular and cellular biology. You should be able to design effective experiments and be able to interpret the results accordingly. Problem-solving abilities and the capacity to drive a research project forward in a pro-active manner are essential as is the ability to work as part of a team. You should be willing to work with category 2 and 3 viruses and supervise and train students. You should have at least one publication as first author in a peer-reviewed journal and be willing to apply for postdoctoral fellowships

The closing date for applications is 12.00 noon on Monday 9 July 2018, with interviews for shortlisted candidates to be held as soon as possible thereafter. Do not hesitate to contact us for further information on this post.


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