Cracking the RNA-binding code of a cell fate regulator

Plasticity in RNA recognition by NHL domains (click to enlarge).
Plasticity in RNA recognition by NHL domains (click to enlarge).
In close collaboration, scientists from the groups of Rafal Ciosk and Helge Grosshans, and the protein structure and computational biology platforms, elucidated the RNA binding rules of LIN41, an important developmental regulator of the self-renewal versus differentiation decision. Interactions between RNA and proteins impact all aspects of RNA metabolism. These interactions are mediated by diverse RNA binding domains (RBDs), of which many remain to be discovered. One example of a recently identified RBD is the NHL domain. This domain is present in so-called TRIM-NHL proteins, like the C. elegans LIN-41 or its human homolog LIN41/TRIM71, collectively referred to as LIN41. How exactly LIN41 proteins recognize specific RNAs remained unknown. Pooja Kumari, one of the authors leading this project, explains: "We knew that the NHL domain mediates the interaction of TRIM-NHL proteins with RNA: The NHL domain of Drosophila Brat binds RNA in a sequence specific manner and our previous work showed that also the NHL domain of LIN-41 mediates the RNA binding.
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