RBPs are key key drivers of gene expression by controlling RNA fate. However, our knowledge about RBPs in plants is very limited. I our recent work, we report an improved RNA interactome capture approach to discover RNA-binding proteins (RBPs) in plant leaves . Using this ‘plant-adapted RNA interactome capture’ (ptRIC) we have identified hundreds novel RBPs, including many enzymes and proteins from the photosynthetic apparatus. ptRIC did not only allowed the generation of the deepest ‘RBPome’ of plant tissue to date, but also opens the possibility to study how the RBPome remodels in response to environmental, physiological and pathological cues.
This work is an interdisciplinary collaborative effort between the Castello lab (Department of Biochemistry) and Preston lab (Department of Plant Sciences) at the University of Oxford. Find out more about this work here:
Our new research published in Molecular Cell has uncovered that virus infection rewires cellular RNA-binding proteins (RBPs) on a global level. This reflects two antagonistic processes: the virus hijacking key cellular resources and the antiviral defence mechanisms of the cell. We discovered dozens of RBPs that play central roles in virus infection and opens new avenues for the development of antiviral therapies. Find out more about this work here.
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.
Our last review was recently published in Nature Reviews – Molecular and Cell Biology. We discuss about the recurrent identification of unorthodox RBPs by proteome-wide methods to identify proteins bound to RNA, and discuss about the potential biological meaning of this exciting discovery.
What can we expect from the discovery of so many new RBPs? Some might side with Miranda from Shakespeare’s The Tempest and marvel at these novel and goodly RBPs that populate the RNA interactome. Others might think of Huxley’s brave new world and fear dystopia, considering the newly discovered RBPs as nonconformist misfits lacking biological function. Which roles do these new RBPs play?
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.