Molecular recognition and RNA-mediated regulation of a bimodular nuclear localization signal – MOBILIS
Nucleo-cytoplasmic transport through nuclear pores is an essential and tightly regulated process in eukaryotic cells. Proteins and multi-component complexes are recognized by transport receptors, called karyopherins. Cargo-receptor interactions are highly specific to ascertain that only fully assembled complexes are being transported across the nuclear membrane.
Transportin-1 (Trn1) is a major nuclear import receptor, known to bind the so-called PY nuclear localization signal (NLS). However many Trn1 cargoes lack a PY-NLS, such as the human RNA-editing enzyme ADAR1. We recently uncovered how an RNA-binding domain in ADAR1 exposes a bimodular NLS, rendering its recognition by Trn1 RNAsensitive.
Here we aim at characterizing the molecular details of the interaction between this atypical NLS and Trn1 using a combination of biophysical, structural, and cellular assays. Moreover, naturally occurring cellular or viral RNAs that specifically interact with ADAR1 in the nuclear or cytoplasmic compartment will be isolated and tested for their ability to modulate the nucleo-cytoplasmic transport of ADAR1. Our studies will yield a detailed understanding of the rules governing the recognition of this novel, non-linear NLS by Trn1 and its regulation by RNA-binding. Moreover, this will shed light on the dual function of ADAR1 as an editing enzyme both fighting viral infections and modifying endogenous RNAs.
Project coordination
Pierre Barraud (Laboratoire d'expression génétique microbienne)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
Partner
UMR8261 Laboratoire d'expression génétique microbienne
MedUni Wien Medical University of Vienna
Help of the ANR 178,048 euros
Beginning and duration of the scientific project:
December 2016
- 36 Months